( 12 ) United States Patent

US010265349B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 265 ,349 B2 Chatila et al. (45 ) Date of Patent: Apr. 23 , 2019

( 54 ) THERAPEUTIC MICROBIOTA FOR THE (56 ) References Cited TREATMENT AND /OR PREVENTION OF FOOD ALLERGY U . S . PATENT DOCUMENTS 5 , 225 , 202 A 7 / 1993 Hodges (71 ) Applicants : THE BRIGHAM AND WOMEN ' S 5, 733 ,575 A 3 / 1998 Mehra HOSPITAL , INC . , Boston , MA (US ) ; 5 , 951, 977 A 9 / 1999 Nisbet CHILDREN ' S MEDICAL CENTER 6 , 139 , 875 A 10 /2000 Adams 6 ,420 ,473 B1 7 / 2002 Chittamuru CORPORATION , Boston , MA (US ) 6 ,455 ,052 B1 9 / 2002 Marcussen 6 , 569, 457 B2 5 /2003 Ullah (72 ) Inventors : Talal A . Chatila , Belmont, MA (US ); 8 , 460, 648 B2 6 / 2013 Borody 8 ,486 ,668 B2 7 /2013 Ritter Lynn Bry , Jamaica Plain , MA (US ); 9 ,011 , 834 B1 4 / 2015 McKenzie et al . Georg Gerber , Boston , MA (US ) ; Azza 9 ,408 , 872 B2 8 / 2016 Borody Abdel -Gadir , Boston , MA (US ) ; Rima 9 , 433 ,652 B2 9 /2016 Honda et al. Rachid , Belmont, MA (US ) 9 ,642 , 882 B2 5 / 2017 Honda et al. 9 ,662 , 381 B2 5 / 2017 Honda et al . 10 ,052 ,353 B2 8 / 2018 Honda et al . (73 ) Assignees: THE BRIGHAM AND WOMEN ' S 2008 /0131556 A16 / 2008 De Simone et al . HOSPITAL , INC. , Boston , MA (US ) ; 2014 / 0341921 Al 11/ 2014 Honda et al. CHILDREN ' S MEDICAL CENTER 2015 / 0004130 A11 / 2015 Faber 2016 /0158294 AL 6 /2016 Von Maltzahn et al . CORPORATION , Boston , MA (US ) 2016 / 0317653 AL 11/ 2016 Cook et al. ( * ) Notice : Subject to any disclaimer , the term of this 2017 /0165302 A16 /2017 Henn et al. patent is extended or adjusted under 35 U . S . C . 154 (b ) by 0 days. FOREIGN PATENT DOCUMENTS EP 0514551 A1 11/ 1992 (21 ) Appl. No. : 15 /801 ,783 EP 2027863 A1 2 /2009 WO 2001 / 060378 A2 8 / 2001 wo 2002 /018614 A1 3 / 2002 (22 ) Filed : Nov . 2 , 2017 WO 2005 /039597 A2 5 / 2005 WO WO2010062369 * 6 /2010 (65 ) Prior Publication Data Wo 2014 / 121304 AL 8 / 2014 wo WO2014 / 121298 * 8 / 2014 US 2018 /0117097 A1 May 3 , 2018 WO WO2015 /095241 * 12 / 2014 Related U . S . Application Data OTHER PUBLICATIONS Benjamini et al ., “ Controlling the False Discovery Rate: A Practical (63 ) Continuation of application NO and Powerful Approach to Multiple Testing ” , Journal of the Royal PCT/ US2016 / 060353 , filed on Nov. 3 , 2016 . Statistical Society Series B , 57 ( 1 ) 289 - 300 ( 1995 ) . Cole et al. , “ Ribosomal Database Project: data and tools for high throughput rRNA analysis ” , Nucleic Acids Res 42 (Database issue) (60 ) Provisional application No . 62/ 250 , 277, filed on Nov. D633 - 1642 ( 2014 ) . Published online Nov . 27, 2013 . 3 , 2015 . Falony et al . , “ Cross - feeding between Bifidobacterium longum BB536 and acetate - converting , butyrate- producing colon bacteria (51 ) Int . CI. during growth on oligofructose ” , Appl Environ Microbiol 72 ( 12 ) A61K 39 /02 ( 2006 .01 ) 7835 - 7841 (2006 ) . A61K 35 / 742 ( 2015 . 01 ) Gerritsen et al. , “ Intestinal microbiota in human health and disease : A61K 45 /06 ( 2006 .01 ) the impact of probiotics ” , Genes Nutr 6 ( 3 ) 209 - 240 (2011 ) . A61K 35 / 74 ( 2015 . 01) (Continued ) A61K 35 / 741 ( 2015 .01 ) A61K 35 / 744 ( 2015 .01 ) Primary Examiner — Jennifer E Graser A61K 35 /745 ( 2015 .01 ) (74 ) Attorney , Agent, or Firm — Nixon Peabody LLP ; A61P 37/ 08 ( 2006 .01 ) David S . Resnick ; Mark J. FitzGerald A61K 9 / 00 ( 2006 . 01) A61K 9 / 19 ( 2006 .01 ) (52 ) U . S . CI. (57 ) ABSTRACT CPC ...... A61K 35 / 742 (2013 . 01 ) ; A61K 9 /0053 Disclosed are methods and compositions for the prevention (2013 .01 ) ; A61K 35 / 74 ( 2013 .01 ); A61K and treatment of food allergy . In particular, described herein 35 /741 (2013 . 01 ) ; A61K 35/ 744 ( 2013 .01 ) ; are microbial consortia , including minimal microbial con A61K 35 / 745 (2013 .01 ) ; A61K 45 / 06 sortia , that can prevent and/ or cure food allergy. In certain ( 2013 . 01 ) ; A61P 37 / 08 ( 2018 .01 ) ; A61K 9 / 19 embodiments , the consortia comprise certain members of (2013 . 01 ); YO2A 50/ 473 (2018 .01 ) the taxa Clostridiales and /or Bacteroidetes. (58 ) Field of Classification Search None See application file for complete search history. 27 Claims, 52 Drawing Sheets US 10 , 265, 349 B2 Page 2

References Cited Open Biome FMT capsules F30 and G3: available on the web at (56 ) openbiome. org / fmtcapsules / . Petrof et al . , “ Stool substitute transplant therapy for the eradication OTHER PUBLICATIONS of Clostridium difficile infection : ' RePOOPulating the gut” ,Microbiome 1 ( 1 ) 3 ( 2013 ). Schloss et al. , “ Introducing mothur: open - source , platform Helm et al. , “ A neonatal swine model for peanut allergy ” , J Allergy independent, community - supported software for describing and Clin Immunol 109 ( 1 ) 136 - 142 (2002 ) . comparing microbial communities ” , Appl Environ Microbiol 75 ( 23 ) Kozich et al. , “ Development of a dual- index sequencing strategy 7537 - 7541 ( 2009 ) . and curation pipeline for analyzing amplicon sequence data on the Smith et al. , “ The microbial metabolites, short -chain fatty acids, MiSeq Illumina sequencing platform ” , Appl Environ Microbiol regulate colonic Treg cell homeostasis ” , Science 341 (6145 ) 569 79 ( 17 ) 5112 -5120 ( 2013 ) . 573 (2013 ) . Lara - Villoslada et al. , “ Short- chain fructooligosaccharides, in spite Yamashita et al ., “ Production of alpha - linked galactooligosac of being fermented in the upper part of the large intestine , have charide (alpha - GOS ) by alpha- galactosidase from Aspergillus niger APC -9319 and its physical and physiological properties ” , Journal of anti - inflammatory activity in the TNBS model of colitis ” , European Applied Glycoscience 51 ( 2 ) : 115 - 121 ( 2004 ) . English Abstract Journal of Nutrition 45 (7 ) 418 -425 ( 2006 ). Only . Mathias et al. , “ IgE -mediated systemic anaphylaxis and impaired Faith et al ., “ Identifying Gut Microbe -Host Phenotype Relation tolerance to food antigens in mice with enhanced IL - 4 receptor ships Using Combinatorial Communities in Gnotobiotic Mice ” , Sci . signaling ” , J Allergy Clin Immunol 127 ( 3 ) 795 -805 ( 2011 ) . Transl . Med . 6 ( 220 ) : 220ra11 ( 2014 ) . Matsen et al ., " pplacer: linear timemaximum - likelihood and Bayes Kailasapathy et al. , “ Survival and therapeutic potential of probiotic ian phylogenetic placement of sequences onto a fixed reference organisms with reference to Lactobacillus acidophilus and tree ” , BMC Bioinformatics 11 :538 ( 2010 ) . Bifidobacterium spp ” , Immunology and Cell Biology 78 : 80 - 88 Mcmurdie et al. , " phyloseq : an R package for reproducible inter ( 2000 ) . active analysis and graphics of microbiome census data ” , PLoS One Prakash et al ., " Gut microbiota : next frontier in understanding 8 ( 4 ) e61217 ( 2013 ) . human health and development of biotherapeutics” , Biologics : “ Medical Physiology /Gastrointestinal Physiology / Secretions” , avail Targets and Therapy 5 :71 - 86 (2011 ) . able at: en .wikibooks . org /wiki / Medical _ Physiology /Gastrointestinal Hopkins et al. " Changes in predominant bacterial populations in Physiology /Secretions ( Printed Feb . 8 , 2018 ) . human faeces with age and with Clostridium difficile infection ” , Noval Rivas et al. , “ A microbiota signature associated with experi Journal of Medical Microbiology 51 ( 4 ) : 448 -452 (2002 ) . mental food allergy promotes allergic sensitization and anaphy Song et al. ““ “ Bacteroides goldsteinii sp . nov. ” isolated from clinical laxis ” , J Allergy Clin Immunol 131 ( 1 ) 201- 212 (2013 ) . specimens of human intestinal origin . " , Journal of Clinical Micro Noval Rivas et al. , “ Regulatory T Cell Reprogramming toward a biology 43 ( 9 ) : 4522 -4527 ( 2005 ) . Th2 - Cell - like Lineage Impairs Oral Tolerance and Promotes Food Allergy ” , Immunity 42 ( 3 ) 512 -523 ( 2015 ) . * cited by examiner U . S . Patent Apr . 23 , 2019 Sheet 1 of 52 US 10 , 265, 349 B2 ooooootruturarteanUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUU DC Mast Cell

ILC2 ILC2

oooos

FIG . 1 atent Apr. 23 , 2019 Sheet 2 of 52 US 10 , 265, 349 B2

. ITIM(Y->Mutationmice:4raF709IL- GainoffunctiontheIL-4R

IL-4Ra )IL-4Ra PPPPPPPPPPPPPPPPPPPPPP FIG.2

(IL-4 IL-4and13Geneexpression

mi OO JAKU OUT Proliferation Differentiation yor are

: STATO TypeIIL-4R: STATG Nucleus atent Apr. 23 , 2019 Sheet 3 of 52 US 10 ,265 , 349 B2

Temperaturedrop -OVAspecificIgEserum -MastcellscountsSI (5mgOVA) -TotalIgEserum Challenge -MCP1

(250ug/10ug) 3 FIG.3 OVA-SEB WeeksOS

DOOR

Y MY poo Www DOOR toooo w DolgoDOG

DopoCOOR

. WTmice PEN

89103 tent Apr . 23 , 2019 Sheet 4 of 52 US 10 ,265 , 349 B2

OVA SEB SEB Let PBSOVA PBS LPF/ cells Mast Nbr )ml / ug ( 1 - MMCP 114raF709 OVA SEB OVA SEB AWT PBS PBS )ml / ug ( IgE Total )ml / ug ( IgE- OVA FIG.4

114raF709+OVA-SEB Time(min) 6050403020100 WT+PBS SEBOVA-WT+O #114raF709+PBS

) °C( Temperature A U . S . Patent Apr . 23 , 2019 Sheet 5 of 52 US 10 ,265 , 349 B2

OVA SEB SEB UPBSOVA PBS ------LLLLLL 2.57 2.04T Na mana mana o ) x104 ( 1l4raF709 IFN + CD4 % IF + CD4 Nbr

SEB SEB WT2.

PBSOVA nh LOPBSMOVA FIG.4(cont) ) x105 ( 41 - IL + CD4 % + 4- IL *CD4 Nbr

GOTOVO 1.6+0% oolella 1.5+04%

OVA-SEB . ?????????????? IFN-Y olisikolloids IL4raf709 10*.3?02% buildinBucurestil. itustilul huuksusluk 01707675,%bullulilu .Judulluisul BAY Y U . S . Patent Apr . 23 , 2019 Sheet 6 of 52 US 10 , 265, 349 B2

IL4raF709OVA-SEB

WeWO Spleenwwwwwwwwwwwwwwwww 15.1+04% LUVY 8.7+01% WIDA maryamsportgagerieor ola ginagamitngayong777TTTT ?????????????????????????????????????????????????????????????????????????????????????????????????????.

w Mindenkinek

yugaypornstagram 15.7+04% 11.8+02% FIG.5 To HURRUNARWARNA rozrzyropinsiranega Tryz7777 wwwwwwwwwwwwwwww hinding . ????? ??????????????????????????????????????? Lliuliteli TO M ww w LU Y AAAA YU JURUUUUUUU

. UUUUUUU

14.9+08% WUUUUUUUUUUUUUU. gumagarityo

! atent Apr. 23 , 2019 Sheet 7 of 52 US 10 ,265 , 349 B2

Spleen PBSOVA SEB

SEB |4raF709 PBSOVA FIG.5(cont) 2.57 1.5 0.517 OWT SEB PBSOVA SIMLN *0.5||E|F 1.57 (901x ) + Foxp3 +CD4 Nbr atent Apr. 23 , 2019 Sheet 8 of 52 US 10 , 265, 349 B2

BOLON 4 , 2 + 0 . 3 % wwt ??????? Simonininni 292 00 **** Foxp3 *

?????? . WY

olului . Juus logo UU. 00000

033 .ww ...... : ......

...... 2000 HUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUU winnininkriminimivimindahandusmärtandininin ...... *XXXXXXXX VAAVAA Counts Beddelantadadadadadadadadadadadadadadada

...... *

......

...... x brow ......

...... X X

???????????? BUSS 1 luchaminimiviminaleinkinimäki modestis Rote . . . LL.3 Cell Trace arvoreViolet FIG . 5 ( cont. ) U. S . Paten atent Apr. 23 , 2019 Sheet 9 of 52 US 10 ,265 , 349 B2

%CD4+Foxp3

PBS OVA SEB

%Prolif.CD4+Foxp3

PBS OVA SEB DWT || 4raF709

FIG . 5 ( cont. ) U . S . Patent Apr. 23, 2019 Sheet 10 of 52 US 10 , 265 , 349 B2

Bacteroidetes Firmicutes

. US

mm -PorphyromonadaceaeM12113CL(48689) LachnospiraceaeRuminococcus(4721) Lachnospiraceaeadhutec250CL(2727) . RuminococcaceaeUnclassified(35554) LachnospiraceaeC18209CL(1003) RikenellaceaellUnclassified(46312) CatabacteriaceaeC1)102(38756 3 FIG.6 2.A RikenellaceaellC20a11(46187) Rikenellaceaellc9E14CL(46257) RikenellaceaellC40241(46591) RikenellaceaellM35082(48287) ClostrodialesUnclassified(1727) -RikenellaceaellUnclassified(45980) -Rikenellaceaellrc215CL(45444)2 -LachnospiraceaeEubacterium(3887) -Rikenellaceaellrcs47CL(46111) Lactobacillaceae(9680) Clostridiaceae(39405) Faecalibacterium(36928) Catabacteriaceae(38832) C A UUD s12}

--- . *. . OLessabundant 59Moreabundant Taxonrelativeabundance *Bacteroidetes*Elusimicrobia &FirmicutesProteobacteria *** * * *birtist Wow **

Rikenellaceae(46917)CM Rikenellaceae(48153) Bacteroidaceae(44071) Saprospiraceae(12142) 3 Pegtostreptococcaceae(41031)- Helicobacteraceae(59023) UnclassifiedNB1CL(55191) UnclassifiedB38(18934) UnclassifiedRSM47(13243) pot LachnospiraceaeC2200G(1405) LachnospiraceaeRF6(42301) LachnospiraceaeM10122CL(1920) LachnospiraceaeRsF27CL(6153) LachnospiraceaeM21506CL(5963) LachnospiraceaeF24FIOCL(5512) LachnospiraceaeC23c19CL(3204) LachnospiraceaeC13P19CL(2293) ]4raf709PBS- LachnospiraceaeEubacterium(6808) ClostrodialesUnclassified(3739) LacinospiraceaeJohnsonella(3508) LachnospiraceaeClostridium(6052) LachnospiraceaeCoprococcus(2933)

2 . 1 de

1 Bacteroidetes Proteobacteria roho Elusimicrobia Firmicutes U . S . Patent Apr. 23 , 2019 Sheet 11 of 52 US 10 ,265 , 349 B2

HH (150mgOVA) Challenge0 8

(100ug) 54 Weeks

1 Microbiota Tor mice FIG.7

WTORJ4raF709 pogo mice U . S . Patent Apr . 23 , 2019 Sheet 12 of 52 US 10 ,265 , 349 B2

Week8 OWTGF+WTFlora IWTGF+114raF709Flora M - ?????? )ml / ug ( 1 - mMCP

FIG.8

Time(min) OVAChallenge:150mg 0102030405060 WTGF+I14raF709Flora OWTGF+Flora

) °C( Temperature A U . S . Patent Apr . 23, 2019 Sheet 13 of 52 US 10, 265 , 349 B2

SW 2 . Gated on2 proliferating10000 od2000 CD329 . . 23 + CD4 + 1 cells: WT GF - OOON114raF709 Flora VINY 0000 MO CAS 0. 78 1036.89

IL-4

28 WS 0833 8. 72 panganggo nofannyen popping me103 104 105

* * *

%IFN-pt %IL-4* odoo

OWT GF + WT Flora IWT GF + 114raF709 Flora

FIG . 9 uus.paten atent Apr. 23 , 2019 Sheet 14 of 52 US 10 ,265 , 349 B2

{}???1

: 100000

- 8

PogoODOO 4o Ma

w 3

TV 2 1GFJ4raf709 mice FIG.10 Microbiota LA Hea Il4raF709NeNOVO U . S . Patent Apr . 23 , 2019 Sheet 15 of 52 US 10 , 265, 349 B2

.0 . 51 ATemperature(°C) -0 . 5 /00000gogoo . 5 -2 . 0 NO-2 . 00 10 20 30 40 50 60 Time (min ) 0 l/ 4raf709 GF + WT Flora || 4raF709 GF + 114raF709 Flora FIG . 11A

TotalIgE(ug/ml) OVA-IgE(ug/ml) 0. 241

LLLLL

/ /4raF709 GF + WT Flora 114raF709 GF + 1l4raF709 Flora FIG . 11B U . S . Patent Apr. 23, 2019 Sheet 16 of 52 US 10 , 265 , 349 B2

114ra F7091 GF Yound referWT Flora VE* 1 /4raF709 Flora wo poona 109 16 . 1 %

WWW www.nhsulotlari VAR samod wybuilu moduliniul IFN -Y FIG . 11C

CD4+IFN-y CD4+IL-4

%OVA-specific %OVA-specific -

0 || 4raF709 GF + WT Flora 114raF709 GF + 1/ 4raF709 Flora FIG . 110 U . S . Patent Apr. 23, 2019 Sheet 17 of 52 US 10 , 265 , 349 B2

114raf709 GF BootsOxong MONO ou * WT Flora + 114raF709 Flora

*few

Foxp3 o zainalitná 090 WS 00 772773- * * * * * www777777777ETIT577777" ** TTTTTTTT CD4 FIG . 12A

NAN NbrCD4+Foxp3 %CD4+Foxp3 OÑO (x105) D // 4raF709 GF + WT Flora 114raF709 GF + 114raF709 Flora

FIG . 12B. . . U . S . Patent Apr. 23, 2019 Sheet 18 of 52 US 10 , 265 , 349 B2

Live CD4 + Foxp3 +

1/ 4raF709 GF ou Sess WT Flora + 114raF709 Flora 1 mah 64. 3 % U 35. 1 %

w www

* We

Susuduusuduusuduusuduusuduusuduusuduusuduusuduusuduusule SwaSabun TH ME mm VVURURUTURUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUUWWWwwwwwwwwwwwV Rt

Violet Proliferative: 37: m Dye FIG . 12C

%ProliferatingCD4+Foxp3

4raF709 GF + WT Flora || 4raF709 GF + || 4raF709 Flora FIG . 12D atent Apr. 23 , 2019 Sheet 19 of 52 US 10 ,265 , 349 B2

FIG.13 Duodenum

0000 Bacteria;Deinococcus-Thermus0% Bacteria;Actinobacteria0% Bacteria;Firmicutes26% Bacteria;Spirochaetes0% Bacteria;Tenericutes0%Bacteria;Verrucomicrobia0% Bacteria;Aquificae0% OBacteria;Bacteroidetes39% DBacteria:Deterribacteres20% OBacteria;Fusobacteria0% OBacteria;Proteobacteria13% Bacteria;TM72% DBacteria;unclassified0% LADA U . S . Patent Apr. 23, 2019 Sheet 20 of 52 US 10 , 265 , 349 B2

FIG.14

WS nnnnnnnnnnnnnnnnnnnnnnnnn

TaxaLineage••••••••• P13

•

OVA,jejunumOtu000850.00380028011608-05BacteriaBacteroidetesBacteroidiaBacteroidalesPorphyromonadaceaeunclassified OVA,jejunumOtu001050.0108003898000534BacteriaFirmicutesClostridiaClostridialesLachnospiraceaeunclassified OVA,jejunumOtu000010.0907054525015739BacteriaFirmicutesClostridiaClostridialesLachnospiraceaeunclassified OVA,jejunumOtu001200.0907006877001008BacteriaFirmicutesClostridiaClostridialesLachnospiraceaeunclassified OVA,jejunumOtu001850.09190035691308-05BacteriaFirmicutesClostridiaClostridialesLachnospiraceaeunclassified OVA,jejunumOtu004590.0919280E-05500E06BacteriaFirmicutesClostridiaClostridialesLachnospiraceaeunclassified OVA,jejunumOtu000410.0919004207000545BacteriaFirmicutesClostridiaClostridialesRuminococcaceaeOscillibacter OVA,lleumOtu000420.0602009597180E-05BacteriaBacteroidetesBacteroidiaBacteroidalesPorphyromonadaceaeunclassified ?OVA,lleumOtu000570.060201515000218BacteriaBacteroidetesBacteroidiaBacteroidalesPorphyromonadaceaeunclassified Otu001070.0602004906000155BacteriaBacteroidetesBacteroidiaBacteroidalesPorphyromonadaceaeunclassifiedOVA,leum OVA,DuodenumOtu(00850.0161004071100E-04BacteriaBacteroidetesBacteroidiaBacteroidalesPorphyromonadaceaeunclassified 836 nnnnnnn OVA,lleumOtu000630.0602019059000216BacteriaBacteroidetesunclassified . .

Bunde 5

F709|WpValue!le-OTUIDGroups| U . S . Patent Apr. 23, 2019 Sheet 21 of 52 US 10 , 265 , 349 B2

•Clostridia *Bacteriodetes *Proteobacteria Oooooooo

AMAMAMAMAMAMAYAMAMMAMMA 8 Challenge(150mgOVA) . . . . 7

100 Y OVA-SEB (250ug/10ug) 45 Weeks83 FIG.15 Pod

1 Antibiotics for7days www. .

TIT IL4raF709mutantmiceMOOOO U . S . Patent Apr . 23 , 2019 Sheet 22 of 52 US 10 ,265 , 349 B2

ATemperature(°C) * * * * enNo Bacteria O Clostridia om the Proteobacteria Bacteriodetes 0 10 20 30 40 50 60 Time (min ) FIG . 16A

mengine No Bacteria C - Clostridia Proteobacteria Bacteriodetes

* * *

NbrMastcells/LPF MMCP-1(ng/ml) 8801 2007 en FIG . 16B U . S . Patent Apr . 23 , 2019 Sheet 23 of 52 US 10 ,265 , 349 B2

No bacteria Clostridia Proteobacteria Bacteriodetes

02 WO Soum 50um FIG . 16C

No Bacteria C - Clostridia Proteobacteria Bacteriodetes * * * *

* * * *

wwwwwwwwwvio TotalIgEug/ml hononoomnomnonood loonanono OOOOOOOOOOOK

S FIG . 16D atent Apr. 23 , 2019 Sheet 24 of 52 US 10 ,265 , 349 B2

/4raF709 IIOWT ????? * OVA SEB minerinnerannomine SEB PBSOVA LLLLLLL AS Foxp3 + CD4 ) 105 *( * 4 - IL among 44- IL of % + Foxp3 + CD4 Nbr FIG.17

4raF709+OVA-SEB WijuOVA-SEB

%L'O 1.9% MLNCO3+CD4 3.% 113 * N19 *. 1 ** ! wwwwwwwwwwwwwwwwwwwwwwwwwwwww

* * KYYTTWTTTM-TTTTTTT7793 Net

1098.5% 1057.8%

Pogoo .boo U . S . Patent Apr. 23, 2019 Sheet 25 of 52 US 10 , 265 , 349 B2

SEB * PBSOVA OWT 1/4raF709

- - - * Foxp3 *CD4 among ) ' 10 *( * Foxp3 *GATA3 of % +CD4 GATA3 of Nbr

1 3-GATA Sooooo NONTON FIG.17(cont)

1.5% ?????????????? 12.4% 29 rrrrrrrrrrrrrrr Siir OVA-SEB ?????-??????????*??? XWOT

3 nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn 10913.5% 1058.9% wwwwwwwwwww MO NO

0.3% 0.8% Www .

PBS indunganITTIFIT S

100f13.1% siissshomantikulminirdischen was wurminnelund 3 11 5 69

nen EdXOJ U . S . Patent Apr. 23, 2019 Sheet 26 of 52 US 10 , 265 , 349 B2

SEB PBSOVA OWT •Il4raF709 *Foxp3 * CD4 ) x105( +Foxp3 among + IRF4 of % +CD4 * IRF4 of Nor

IRF-4 gor E FIG.17(cont)

2.8% L'%

OVA-SEB T 1 .24

www 108-9.4% U Sa 2 %LEL,010€ IRF4 UE01%- TO 3.9%

13.6%

LUX

3 U . S . Patent Apr. 23 , 2019 Sheet 27 of 52 US 10 , 265, 349 B2

-9.99 IIII 13A/A141Foxp3EGFPCreAll4raF709 102030405060 Time(min) FIG.18B LPF/ cells mastNbr

??? ??????0 ) °C( Temperature A 114raF709 )ml / ug ( 1- MMCP FIG.18C

CD4+ Foxp3-Foxp3t FIG.18A )ml / ug( IgE- OVA

Change Fold 7 . . . H

)ml / ug( IgE Total U . S . Patent Apr. 23 , 2019 Sheet 28 of 52 US 10 , 265, 349 B2

UA - 0114raF709Foxp3EGFPCre|14/1134A * L . o *La Has 18F.FIG ) 105 ( + 4 - IL * 4- IL -Foxp3 +CD4 % Foxp3 +CD4 4raF709•

oll4raF709Foxp3EGFPCre114/11134A miniini FIG.18E * Foxp3 * CD4 +Foxp3 * CD4 3tamong - GATA % among 41- IRF % •Il4raF709

o114raF709Foxp3EGFPCre|14/11344 upepo uroBasics FIG.18D

•Il4raF709 *Foxp3 +CD4 % ) x106( + Foxp3 + CD4 U . S . Patent Apr. 23, 2019 Sheet 29 of 52 US 10 , 265 , 349 B2

CO3 + CD4 +

u N No Bacteria IT

* * * - VS * * * * p ririman VV €

%CD3+CD4FOXP3 A Clostridia

Foxp3 pomen parties impompinigaigai proponang * * * * YOU * * *

Proteobacteria . PI ***** . 1.

w NbrCD3+CD4Foxp3(x105) .

PORT bestellen duten behar OOO i * VVVY

Bacteriodetes

WOOD AN FIG . 19 U . S . Patent Apr. 23, 2019 Sheet 30 of 52 US 10 , 265 , 349 B2

CD3 + CD4 +

MA * * * * 2. 28 wa * * * * business.de %1L4+Foxp3 udbruk

???? ???????????????? ?????? M Foxp3 Pont

* * * *

W %GATA3+Foxp3 TTTT

0 .0884

0000 de immlisciandolimesthitimbulkaistumkrets

A FIG . 19 (.cont . ) UU. S. S. . Patent Patent manApr . 23som , 2019 Sheetmees 31 of 52 USus 10wako ,265 , 349 B2

???? OVA SEB •ll4raF709 80,Acetate OWT mM 016OVA SEB o Boto OVA SEB FIG.20A PBS PBS 1.5,Valerate 15,Butyrate Wu W

. . OVA SEB SEB 1.57Isolvalerate PBS 20,Propionate UPBSOVA wu wu atent Apr. 23 , 2019 Sheet 32 of 52 US 10 ,265 , 349 B2

1/4raF709

IIIIIIIIIIIIIIIIIIIIIIIIII

%92 OVA-SEB+SCFAS www

LI V ? W PAD WVVO M

FIG.20A(cont.) PBS+SCFAS 290090ogooooooo www 6.7%

Co wwwwwwwww . 1 1 ws w w VVV

12.2%

. OVA-SEB www .

Laitu fure Mah MAS ann Foxp3 U . S . Patent Apr . 23 , 2019 Sheet 33 of 52 US 10 ,265 , 349 B2

SEB SEB PBSOVA SCFAS Ohool PBSOVA SCFAS 8944 %

Toto OVA SEB OVA SEB

FIG.20B

0102030405060 Time(minutes) l/4raF709OVA-SEB+SCFAS +Il4raF709PBSSCFAS OWTOVA-SEB+SCFAS +14raF709OVA-SEB OWTPBS+SCFAS *WTOVA-SEB

) °C( Temperature A U . S . Patent Apr. 23, 2019 Sheet 34 of 52 US 10 , 265 , 349 B2

. * .

. .

IgE(ug/ml) .

. . .

. ]Spe . . etter.

. . . —oplo . . .

. 1 SHOT 1

. . PBS OVA .

. SEB

. . * SCFAS O WT . 7 . || 4raF709

OVA-IgE(ug/ml) t * NDNDO OVA PBS OVA SEB SEB SCFAS

FIG . 20C U . S . Patent Apr . 23 , 2019 Sheet 35 of 52 US 10 ,265 , 349 B2

NoBacteria oClostridiales *Bacteriodetes Proteobacteria v oce * * * * wwwwwwwwwwwwwwwwww

P . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 2

Door 000 Weeks man ? < FIG.21A 102030405060 Time(min) FIG.21B 4 Proteobacteria)Control(Negativeor OVA-SEB orGP-II(Bacteriodetes) GP-1(Clostridiales) ( *0 ws Antibiotics ) °C( ATemperature U . S . Patent Apr. 23, 2019 Sheet 36 of 52 US 10 , 265 , 349 B2

NoBacteria Clostridiales Bacteriodeles Proteobacteria

FIG.21D

ODDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDD Bacteriodetes

)ml W/ ng ( 1- MMCP

Proteobacteria DDDDDDDD FIG.21E

OOOOOO Clostridia 100001 05000 )ml / ng ( IgE OVA FIG.21C NoBacteria

* O 7010 ml/ ug IgE Total atent Apr. 23 , 2019 Sheet 37 of 52 US 10 ,265 , 349 B2 ??????????????

Bacteriodetes . . , . merr - za - s parrini ms

. VI . . .

. bilgiyegelenwerden

. Proteobacteria :) CD4 GatedonCD4+Foxp3 FIG.21F * 000 FIG.216 w Food + Foxp3 + C04 % Clostridia 1.53 en 1

. Lammutamise

XA wa 4.53

NoBacteria * * * *

+ come

hite w

Sound U . S . Patent Apr. 23, 2019 Sheet 38 of 52 US 10 , 265 , 349 B2

0.32 mawakalandic 12

2.35

bawah di industriale youtube AY

0.2610

Proteobacteria * * * * quagterrapepparempaqueporrogespanama MRTI 0.11109274 nnnn .. FIG.21H FIG.211 mudelilabad > + 1L4 + Foxp3 %

tow

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0.2310224 YVU YVVIVE

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1091.35 atent Apr. 23 , 2019 Sheet 39 of 52 US 10 ,265 , 349 B2

NoBacteriaOVA/SEB ClostridialesPBSClostridialesOVA/SEB BacteriodetesPBS +BacteriodetesOVA/SEB

Got 5 Won

3 FIG.22A 2030405060 FIG.22B

5 Time(min) 14: GPIlcommunities3:1375 1 OVA-SEB 10

0 ) °C ( ATemperature U . S . Patent Apr. 23, 2019 Sheet 40 of 52 US 10 , 265 , 349 B2

No Bacteria Clostridiales * PBS D Clostridiales + OVA /SEB Bacteriodetes + PBS Bacteriodetes + OVA /SEB * * * *

0100100100100100100100100100100100100100100 OOOOOOOOOOOOOOOOOOOOOOOOOOO 300007 600010CHOKKOKKOKKOKO ? ooooooooooooooo (ng/ml) TotalIgEng/mlà . 20000 pomo8 24000 ?? OVAIGE5200 000000000000000000000000000000000DDDD ollados

FIG . .22C

w * * 200007 * O No Bacteria MMCP-1(ng/ml) D Clostridiales + PBS 1500048 Clostridiales + OVA / SEB 10000I Bacteriodetes + PBS 500019bebes Bacteriodetes + OVA /SEB FIG. . 22D U . S . Patent Apr. 23, 2019 Sheet 41 of 52 US 10 , 265 , 349 B2

turi . OVA/SEB . w Clostridiales+OVA/SEB Bacteríodetes ?? ?????????????????????????????? Y PBSBacteriodetes+ OClostridiales+PBS Bacteriodetes+OVASEB Bacteriodetes ????????????? ONoBacteria hotellectuellementodlochoren N oooooooooooooooooooooo. ku **

OVA/SEB , oooo 2.44 FIG.22E 87nga FIG.22F Clostridiales + Foxp3 + CD4 + CD3 % issemantikasuhinakailanmaktacounting ind 3 MODO DO DO

* ClostridialesPBS ????????????? ???????????????????????????????????? DDDDDDDDDDDDDDDDD ?????? ????? ?????? ?? V U V YOO + CD4 + CD3 % ?????? NoBacteria OVASEB ?????????

kasalmentingmenduduki indadasal minimarkadasl ortamlardakta * * * 0 Foxp3 U . S . Patent Apr. 23, 2019 Sheet 42 of 52 US 10 , 265 , 349 B2

JOLL.083_LLO

- NK Segundo

2 094.1luke.Blowbanden hari1700 - tyt Bacteriodetes+OVA/SEB 0.8310354 w DClostridiales+OVA/SEB 4.04duenbe DClostridiales*PBS DBacteriodetes+PBS NoBacteria

stelonkeBolo w

0.48104327 w 5.670919 Luxu. 2 . LL30 FIG.22G FIG.22H

0.5410-181 wand pon + Foxp3 + IL4 % YYYYYYYYYYYYYYYYY 6.91092 uit. BesorgenSousses.

$11,01 Bulacanervosa Bioloooo 0 OOOOOOOOOOOOOOOOOOOOO w 2.Suacil + Foxp3+ IFNY %

with |87101 disabilitation w U . S . Patent Apr. 23 , 2019 Sheet 43 of 52 US 10 , 265, 349 B2

Clostridiales orghinProteobacteria &Bacteriodetes 1112 pogo

9 M Antibioticswwww GP-1,IIorNCCconsortia 2030405060 FIG.23A Time(min) FIG.23B

OVA-SEB"1 10

WEEKS 0 ) °C ( ATemperature U . S . Patent Apr . 23 , 2019 Sheet 44 of 52 US 10 , 265, 349 B2 Clostridiales Proteobacteria Bacteriodetes Clostridiales Proteobacteria Bacteriodetes O D O OOHO FIG.23D ooooooooooooo FIG.23F 007 O 000 HULLULLLLLLL 5000 FOXP3 + CD4 %

1000040 w )ml / ng ( 1 - MMCP 26.5 Bacteriodetes YUVVU. administratiekalasitahidasthmandy Clostridiales Proteobacteria Bacteriodetes AR $9.10' 10 de WUUUUUUUUUUUUU CD4 wwwwwwwwwwww N FIG.23E

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. . uul l luul . . . LULU. SM. . C ml/ ug IgE Total W atent Apr. 23 , 2019 Sheet 45 of 52 US 10 ,265 , 349 B2

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e Bacteriodetes 134 willbein

IFN-Y FIG.23G 13 buitewizohukoBundesliga Proteobacteria . belir 10- . w

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oo Ho )ml / ng ( IgE OVA

. . . 8WEEKSW FIG.240

6 00 DO

5 ml/ ug IgE Total 4 1 FIG.24A 3CA o1 Morg

2 1

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10 Twwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww ) 0 ( Alemperature U . S . Patent Apr . 23 , 2019 Sheet 47 of 52 US 10 ,265 , 349 B2

TULO Bawahbidadaribroddas DNoBacteria Clostridiales OBacteriodetes Va Bacteriodetes poo oculty n luchtisco alcoholmen hautaut Com FIG.24F e ooo -UUUUUUUUUUUUUUUUUUUUUU 0 . . 0 . 0 0 0 0 CD4 FIG.240 Clostridiales besimtahetomherriedenuit + Foxp3 + CD4 % oltinnhanh w dos W . OOO TUUS o amca FIG.24E

NoBacteria TUTUYU aama + CD4 + CD3 % www AAM W Foxp3 U . S . Patent Apr. 23, 2019 Sheet 48 of 52 US 10 , 265 , 349 B2

NoBacteriaw who Clostridiales OCDD Bacteriodetes nnnnnnnnn

* * * * * * * * * * * * * * * * * * * * * * * * CD4FNY % VO FIG.24J

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000000000000000 . 0 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 + Foxp3 + L4 % U . S . Patent Apr . 23 , 2019 Sheet 49 of 52 US 10 ,265 , 349 B2

10NON NoBacteria Clostridiales gelyolculuk MMMMMMMMMMMMMMMMMMMMMMMMMMN.

Bacteriodetes 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 . 0 * r * * *0 7 * * * ort* * * * * * * * * poprugotoxy

010 OOO 000000000000 LILLO

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A OLLO2010 + Foxp3 +Nrp1 + Helios %

TETITVTT 43

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Annan nannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn atent Apr. 23 , 2019 Sheet 50 of 52 US 10 ,265 , 349 B2

F709;NoBacteria PBSF709* OF709+Clostridiales WT*Clostridiales 1112WEEKS

10 HY IOIand forward

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0 . GP-1consortium(Clostridiales) 7

. C 102030405060 6 Time(min)

: FIG.25A : FIG.25B

5 : DOT os

DO 4 : -

3 -

2 0 1 OVA-SEB1litrili ) °C( ATemperature atent Apr. 23 , 2019 Sheet 51 of 52 US 10 ,265 , 349 B2

OF709NoBacteria. WT-+Clostridia ano 0

Tiininnnnnnnnnnnnnn JUU OF709NoBacteria F709-+Clostridia W+-Clostridia Foxp3 + CD4 % FIG.25D ooho ???? COD DOO O raco + CD4 + CD3 % + Foxp3 + IL4 % Ho FIG.25E 00020 NoBacteriaClostridia 000m O + L4 + CD4 %

2 1500 1000L )ml / ng ( IgE OVA FIG.25C o to o lesbo ml/ ug IgE Total atent Apr. 23 , 2019 Sheet 52 of 52 US 10 ,265 , 349 B2

FIG.25G FIG.251

OBESITYSEEEEEEEEEEET Too 00 00 0.017 + 1L17 + CD4 % Foxp3t + IL17

AN paragraph WT+Clostridiales 1 ! C iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiinnor divinisvivienevievaviri VNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN . bui Foxp3 F709-+Clostridiales hoorn FIG.25F F709+Clostridiales FIG.25H 1.83

C Po . CA mo 104

: ......

F709NoBacteria F709NoBacteria AAAAAAAAAAAAAAAAAAAA DOOR 3 VNMNMMMNNNNNNNNNNNNNNNNNNNN nararanasa Whilinhabilidad

00003pood US 10 , 265, 349 B2 THERAPEUTIC MICROBIOTA FOR THE gut bacterial strains that alone or in combination performs TREATMENT AND /OR PREVENTION OF the full complement of bile acid transformations ; (iv ) a FOOD ALLERGY preparation of a viable , culturable , anaerobic gut bacterial strain that produces compounds capable of stimulating the CROSS -REFERENCE TO RELATED 5 aryl hydrocarbon receptor (AhR ) receptor pathway in gut APPLICATIONS epithelial cells , antigen presenting cells and / or T cells to stimulate development of regulatory T cell responses ; ( v ) a preparation of a viable , culturable , anaerobic gut bacterial This Application is a Continuation Application of Inter strain ( s ) that produces compounds capable of stimulating the national Application No. PCT /US2016 / 060353 filed Nov. fit3 , 10 pregnane X receptor with beneficial effects upon gut barrier 2016 , which designates the U . S . and which claims benefit 10 function and / or development of regulatory T cell responses ; under 35 U . S . C . $ 119 ( e ) of the U . S . Provisional Application ( vi ) a preparation of a viable , culturable , anaerobic gut No . 62 /250 ,277 filed Nov . 3 , 2015 , the contents of each of bacterial strain (s ) that produces compounds capable of which are incorporated herein by reference in their entire stimulating the RORgamma (RAR - related orphan receptor ties. 15 gamma) pathways to stimulate development of regulatory T cell responses via direct stimulation or RORgamma- acti GOVERNMENT SUPPORT vated pathways in gut antigen presenting cells and /or epi This invention was made with Government Support under thelial cells that then stimulate regulatory T cell responses ; Grant Nos. 1R56A111798 -01 and P30 DK056338 awarded (vii ) a preparation of viable , culturable , anaerobic gut bac by the National Institutes of Health . The Government has 20 terial strain ( s ) that stimulates host production of mucins and complex glycoconjugates that improve gut barrier function certain rights in the invention . and colonization by protective commensal species ; ( viii ) a FIELD OF THE DISCLOSURE preparation of a viable , culturable , anaerobic gut bacterial strain ( s ) that alters the gut luminal environment to reduce The present disclosure relates to the treatment and /or 25 the deleterious activities of dysbiotic species promoting prevention of food allergy . development of unhealthy allergic T cell responses to food antigens ; ( ix ) a preparation of a viable , culturable , anaerobic BACKGROUND gut bacterial strain ( s ) that alters the gut luminal environment to promote improved colonization by other members of the Food allergies are a growing public health problem in 30 administered consortium for any of the above stated effects , both developed and rapidly developing countries and affects and /or colonization by existing beneficial species in the large numbers of children and adults. The incidence of food patients underlying microbiota ; ( x ) a preparation of a viable , allergy has increased dramatically in the last few decades . culturable , anaerobic gut bacterial strain ( s ) that promotes the This increase can be associated with sensitization to multiple colonization or growth of a bacterial strain in a preparation foods in up to 50 % of subjects . Growing evidence indicates 35 of ( i) - ( ix ) above, in vivo . that the microbial flora is a key environmental influence in In one embodiment of this aspect and all other aspects programming oral tolerance. described herein , the viable , culturable , anaerobic gut bac terial strain ( s ) that expresses exopolysaccharide that pro SUMMARY motes the development of regulatory T cells (Treg ) is 40 selected from the group consisting of: Eubacterium rectale , Provided herein are methods and compositions for the Clostridium ramosum , Butyrovibrio crossatus, Roseburia treatment and / or prevention of food allergy , based in part , on intestinalis , Clostridium scindens, Clostridium hylemonae , the discovery that altered intestinal microbiota ( e. g ., from Hungatella hathawayi, Clostridium symbiosum , Faecali antibiotic treatments , C -section births, diet etc . ) can promote bacterium prausnitzii , Subdoligranulum variabile , Bacte food allergy while some combinations of microbes can 45 roides thetaiotaomicron , Bacteroides fragilis , Bacteroides prevent and /or cure food allergies. ovatus, Parabacetroides goldsteinii, Parabacteroides mer Accordingly , provided herein in one aspect is a pharma- dae , Parabacteroides distasonis , and Prevotella tannerae. ceutical composition comprising : ( i ) a preparation compris - In another embodiment of this aspect and all other aspects ing a minimal microbial consortium consisting essentially of provided herein , the viable , culturable , anaerobic gut bac four to eleven strains of viable gut bacteria , in an amount 50 terial strain ( s ) that produces butyrate , propionate and /or sufficient to treat or prevent a food allergy when adminis - succinate fermentation products via fermentation of carbo tered to an individual in need thereof, and ( ii ) a pharmaceu - hydrates in the gut lumen is selected from the group con tically acceptable carrier. sisting of: Bacteroides fragilis , Bacteroides thetaiotaomi Another aspect provided herein relates to a pharmaceuti - cron , Bacteroides ovatus, Clostridium sardiniensis , cal composition comprising a minimal microbial consortium 55 Clostridium hiranonsis, Face?libacterium prausnitzii, Buty of culturable species , and a pharmaceutically acceptable rovibrio spp ., Eubacterium rectale and Roseburia intestina carrier , wherein the consortium is comprised in at least four l is of the preparations selected from the group consisting of: (i ) In another embodiment of this aspect and all other aspects a preparation of a viable , culturable, anaerobic gut bacterial provided herein , the one or more viable , culturable , anaero strain ( s ) that expresses exopolysaccharide, lipoteichoic acid 60 bic gut bacterial strains that alone or in combination per (LTA ) , lipopolysaccharide (LPS ) or other microbial adjuvant forms the full complement of bile acid transformations is molecules that promote the development of regulatory T Clostridium scindens, Clostridium hiranonsis , Clostridium cells ( Treg ) ; ( ii ) a preparation of a viable , culturable , anaero sardiniensis and /or Bacteroides spp . bic gut bacterial strain ( s ) that produces butyrate and /or In another embodiment of this aspect and all other aspects propionate fermentation products via fermentation of car- 65 provided herein , the viable , culturable , anaerobic gut bac bohydrates and other carbon sources in the gut lumen ; ( iii ) terial strain ( s ) that produces aryl hydrocarbon receptor ago a preparation of one or more viable, culturable , anaerobic nists sufficient to stimulate host aryl hydrocarbon receptor US 10 , 265 , 349 B2 pathways comprises at least one gene associated with the comprises an enteric coating composition that encapsulates synthesis of tryptophan , tyrosine or the synthesis of quinone the minimal microbial consortium . molecules . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the pharmaceutical composition is formu provided herein , the viable , culturable , anaerobic gut bac - 5 lated to deliver the viable bacteria to the small intestine . terial strain ( s ) that promotes the colonization or growth of a In another embodiment of this aspect and all other aspects bacterial strain in a preparation is Bacteroides thetaiotao - provided herein , the enteric -coating composition is in the micron , or Bacteroides fragilis . form of a capsule , gel, pastille , tablet or pill . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the viable , culturable , anaerobic gut bac - 10 provided herein , the strains of viable , culturable , anaerobic terial strain ( s ) that produces compounds endogenously or by gut bacteria are human gut bacteria . metabolizing exogenous precursors , that is capable of stimu- In another embodiment of this aspect and all other aspects lating the pregnane X receptor with beneficial effects upon provided herein , the strains of viable , culturable , anaerobic gut barrier function and / or development of regulatory T cell g ut bacteria are selected from the group consisting of: responses is a strain that expresses desmolase and/ or 15 Clostridium ramosum , Clostridium scindens , Clostridium hydroxysteroid dehydrogenase . In this context, exogenous hiranonsis , Clostridium bifermentans, Clostridium leptum , precursors include not just dietary compounds or factors , but Clostridium sardiniensis , Bacteroides fragilis , Bacteroides also factors produced by the host and excreted into the gut thetaiotaomicron , Bacteroides ovatus, Parabacteroides which are then acted upon by one or more members of a goldsteinii , Prevotella tannerae , Clostridum hathewayi, microbial consortium as described herein . 20 Clostridum nexile , Clostridium hylemonae, Clostridium gly In another embodiment of this aspect and all other aspects cyrrhizinilyticum , Clostridium scindens , Clostridium laval provided herein , the viable , culturable , anaerobic gut bac ense , Clostridum fimetarium , Clostridium symbiosum , terial strain ( s ) that produces compounds endogenously or by Clostridium sporosphaeroides , Dialister proprionicfaceins, metabolizing exogenous precursors , that is capable of stimu - Dialister succinatiphilus, Parabacteroides distasonis, Para lating the RORgamma (RAR - related orphan receptor 25 bacteroides goldsteinii , Parabacteroides merdae , Pepto gamma ) pathways to stimulate development of regulatory T streptococcus anaerobius, Subdoligranulum variabile , and cell responses is a strain that expresses at least one choles - Veilonella ratti . terol reductase or another enzyme capable of metabolizing In another embodiment of this aspect and all other aspects sterol compounds. provided herein , the strains of viable , culturable , anaerobic In another embodiment of this aspect and all other aspects 30 gut bacteria are selected from the group consisting of : provided herein , the viable , culturable , anaerobic gut bac - Clostridium ramosum , C . scindens , C . hiranonsis, C . bifer terial strain ( s ) that is capable of stimulating host mucins and mentans , C . leptum , C . sardiniensis , Bacteroides fragilis , B . complex glycoconjugates that improve gut barrier function thetaiotaomicron , B . ovatus, Parabacteroides goldsteinii , and colonization by protective commensal species is Bacte and Prevotella tannerae . roides thetaiotaomicron or Bacteroides fragilis . 35 In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the strains of viable, culturable , anaerobic provided herein , the viable , culturable , anaerobic gut bac - gut bacteria are selected from the group consisting of: ( i ) terial strain ( s ) that alter the gut luminal environment to Clostridium ramosum , C . scindens, C . hiranonsis , C . bifer reduce the deleterious activities of dysbiotic species that mentans, C . leptum , and C . sardiniensis , or ( ii ) Bacteroides contribute to development of pathogenic allergic T cell 40 fragilis, B . thetaiotaomicron , B . ovatus, Parabacteroides responses to food antigens is Bacteroides thetaiotaomicron , goldsteinii , and Prevotella tannerae. Bacteroides fragilis or another Bacteroides spp . An In another embodiment of this aspect and all other aspects examples includes alterations of the gut environment from provided herein , the strains of viable , culturable , anaerobic Bacteroides species that reduces the biomass of dysbiotic gut bacteria are present in substantially equal biomass . species in the Enterobacteriaceae or Desulfonovibriaceae 45 In another embodiment of this aspect and all other aspects and / or prevent full expression of dysbiotic biochemical or provided herein , the composition is formulated to deliver a microbiologic activities expressed by these species. dose of at least 1x10° colony forming units (CFU ) . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the viable , culturable , anaerobic gut bac provided herein , the composition is formulated to deliver at terial strain ( s ) alter the gut luminal environment to promote 50 least 1x10° CFUs in less than 30 capsules per one time dose . improved colonization by other members of the adminis - In another embodiment of this aspect and all other aspects tered consortium for any of the above stated effects , and / or provided herein , the composition is frozen for storage . colonization by existing beneficial species in the patients In another embodiment of this aspect and all other aspects underlying microbiota is Bacteroides thetaiotaomicron , provided herein , the strain (s ) of viable culturable , anaerobic Bacteroides fragilis , or Bacteroides spp . In another embodi- 55 gut bacteria are encapsulated under anaerobic conditions . ment of this aspect and all other aspects provided herein , the In another embodiment of this aspect and all other aspects beneficial species comprises Clostridium spp ( e . g . , provided herein , the strain ( s ) of viable culturable , anaerobic Clostridium ramosum , Clostridium scindens, Clostridium gut bacteria are lyophilized under anaerobic conditions. hiranonsis , Clostridium bifermentans, Clostridium leptum , In another embodiment of this aspect and all other aspects Clostridium sardiniensis , Clostridium hathewayi, 60 provided herein , anaerobic conditions comprise one or more Clostridium nexile , Clostridium hylemonae, Clostridium of the following : ( i ) oxygen impermeable capsules, ( ii ) glycyrrhizinilyticum , Clostridium lavalense , Clostridium addition of reducing agents including N - acetylcysteine, cys fimetarium , Clostridium symbiosum , Clostridium spo teine , or methylene blue to the composition , and ( iii ) use of rosphaeroides etc .) or another non - pathogenic commensal spores for organisms that sporulate . strain . 65 In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the consortium comprises at least one provided herein , the pharmaceutically acceptable carrier bacterial strain comprising a 16S rDNA sequence at least US 10 , 265 , 349 B2 97 % identical to a 16S rDNA sequence present in a reference In another embodiment of this aspect and all other aspects strain operational taxonomic unit , the reference strain provided herein , the enteric - coating comprises a polymer , selected from the group consisting of: Clostridium ramo - nanoparticle , fatty acid , shellac , or a plant fiber . sum , C . scindens, C . hiranonsis , C . bifermentans, C . leptum , In another embodiment of this aspect and all other aspects and C . sardiniensis , or wherein the consortium comprises at 5 provided herein , the composition further comprises a pre least one bacterial strain comprising a 16S rDNA sequence biotic composition . at least 97 % identical to a 16S rDNA sequence present in a In another embodiment of this aspect and all other aspects reference strain operational taxonomic unit , the reference provided herein , the composition is encapsulated , a recon strain selected from the group consisting of: Bacteroides stituted lyophilisate , a food item , or is formulated as a liquid , fragilis , B . thetaiotaomicron , B . ovatus , Parabacteroides 10 gel , fluid - gel, or nanoparticles in a liquid . goldsteinii , and Prevotella tannerae . Another aspect provided herein relates to a pharmaceuti In another embodiment of this aspect and all other aspects cal composition comprising : (i ) a preparation comprising at provided herein , the consortium does not comprise any of least four strains of viable , anaerobic , culturable gutbacteria the Species Escherichia coli, Klebsiella pneumoniae , Pro - selected from the group consisting of: Clostridium ramo teus mirabilis , Enterobacter cloacae , Bilophila wadswor - 15 sum , Clostridium scindens, Clostridium hiranonsis , thia , Alistipes onderdonkii , Desulfovibrio species, Lactoba - Clostridium bifermentans, Clostridium leptum , Clostridium cillus johnsoni, Parasutterella excrementihominis . sardiniensis , Bacteroides fragilis , Bacteroides thetaiotaomi In another embodiment of this aspect and all other aspects cron , Bacteroides ovatus, Parabacteroides goldsteinii, Pre provided herein , the consortium does not comprise bacteria votella tannerae , Clostridum hathewayi, Clostridum nexile , of the Genera Bilophila , Enterobacter, Escherichia , Kleb - 20 Clostridium hylemonae , Clostridium glycyrrhizinilyticum , siella , Proteus, Alistipes, Blautia , Desulfovibrio , or Para - Clostridium scindens, Clostridium lavalense , Clostridum sutterella . fimetarium , Clostridium symbiosum , Clostridium spo In another embodiment of this aspect and all other aspects rosphaeroides, Dialister proprionicfaceins, Dialister succi provided herein , the consortium does not comprise bacteria natiphilus, Parabacteroides distasonis , Parabacteroides of the Families Desulfovibrionaceae , Enterobacteriaceae , 25 goldsteinii , Parabacteroides merdae , Peptostreptococcus Rikenellaceae , and Sutterellaceae . anaerobius, Subdoligranulum variabile , and Veilonella In another embodiment of this aspect and all other aspects ratti ., in an amount sufficient to treat or prevent a food provided herein , the consortium does not comprise bacteria allergy when administered to an individual in need thereof, of the Families Lactobacillaceae, or Enterbacteriaceae . and ( ii) a pharmaceutically acceptable carrier. In another embodiment of this aspect and all other aspects 30 In one embodiment of this aspect and all other aspects provided herein , the consortium does not comprise bacteria provided herein , the composition comprises not more than of the Order Burkholdales , Desulfovibrionales, or Entero - forty strains of viable , anaerobic , culturable gut bacteria . bacteriales. In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition comprises not more than provided herein , the composition comprises at least five 35 thirty strains of viable , anaerobic , culturable gut bacteria . strains of viable non -pathogenic gut bacteria . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition comprises not more than provided herein , the composition comprises up to eleven twenty strains of viable, anaerobic , culturable gut bacteria . strains of viable non -pathogenic gut bacteria . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects 40 provided herein , the composition comprises not more than provided herein , the composition comprises Clostridium fifteen strains of viable , anaerobic, culturable gut bacteria . ramosum , C . scindens , C . hiranonsis, C . bifermentans , C . In another embodiment of this aspect and all other aspects leptum , and C . sardiniensis . provided herein , the composition comprises not more than In another embodiment of this aspect and all other aspects eleven strains of viable , anaerobic , culturable gut bacteria . provided herein , the composition comprises Bacteroides 45 In another embodiment of this aspect and all other aspects fragilis , B . thetaiotaomicron , B . ovatus, Parabacteroides provided herein , the composition comprises at least five goldsteinii, and Prevotella tannerae . strains of viable, anaerobic , culturable gut bacteria selected In another embodiment of this aspect and all other aspects from the group consisting of: Clostridium ramosum , provided herein , the composition comprises: Clostridium Clostridium scindens, Clostridium hiranonsis , Clostridium ramosum , C . scindens , C . hiranonsis , C . bifermentans , C . 50 bifermentans , Clostridium leptum , Clostridium sardiniensis , leptum , C . sardiniensis , Bacteroides fragilis, B . thetaiotao - Bacteroides fragilis , Bacteroides thetaiotaomicron , Bacte micron , B . ovatus, Parabacteroides goldsteinii , and Pre - roides ovatus, Parabacteroides goldsteinii, Prevotella tan votella tannerae . nerae , Clostridum hathewayi, Clostridum nexile , In another embodiment of this aspect and all other aspects Clostridium hylemonae , Clostridium glycyrrhizinilyticum , provided herein , the bacterial strains in the composition 55 Clostridium scindens, Clostridium lavalense , Clostridum consists essentially of Clostridium ramosum , C . scindens , C . fimetarium , Clostridium symbiosum , Clostridium spo hiranonsis, C . bifermentans , C . leptum , and C . sardiniensis . rosphaeroides, Dialister proprionicfaceins, Dialister succi In another embodiment of this aspect and all other aspects natiphilus, Parabacteroides distasonis , Parabacteroides provided herein , the microbial consortium consists essen - goldsteinii , Parabacteroides merdae, Peptostreptococcus tially of Bacteroides fragilis , B . thetaiotaomicron , B . ovatus, 60 anaerobius, Subdoligranulum variabile , and Veilonella ratti . Parabacteroides goldsteinii , and Prevotella tannerae . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition comprises at least six provided herein , the microbial consortium consists essen strains of viable, anaerobic , culturable gut bacteria selected tially of: Clostridium ramosum , C . scindens, C . hiranonsis , from the group consisting of: Clostridium ramosum , C . bifermentans, C . leptum , C . sardiniensis , Bacteroides 65 Clostridium scindens, Clostridium hiranonsis , Clostridium fragilis , B . thetaiotaomicron , B . ovatus , Parabacteroides bifermentans, Clostridium leptum , Clostridium sardiniensis , goldsteinii , and Prevotella tannerae . Bacteroides fragilis, Bacteroides thetaiotaomicron , Bacte US 10 , 265, 349 B2 roides ovatus, Parabacteroides goldsteinii, Prevotella tan - Clostridium scindens, Clostridium lavalense, Clostridum nerae, Clostridum hathewayi, Clostridum nexile , fimetarium , Clostridium symbiosum , Clostridium spo Clostridium hylemonae, Clostridium glycyrrhizinilyticum , rosphaeroides , Dialister proprionicfaceins, Dialister succi Clostridium scindens, Clostridium lavalense, Clostridum natiphilus, Parabacteroides distasonis , Parabacteroides fimetarium , Clostridium symbiosum , Clostridium spo - 5 goldsteinii . Parabacteroides merdae . Peptostreptococcus rosphaeroides , Dialister proprionicfaceins, Dialister succi anaerobius, Subdoligranulum variabile , and Veilonella ratti. natiphilus , Parabacteroides distasonis , Parabacteroides In other embodiments of this aspect and all other aspects goldsteinii, Parabacteroides merdae , Peptostreptococcus anaerobius, Subdoligranulum variabile, and Veilonella ratti. provided herein , the composition comprises a range of 4 - 28 , In another embodiment of this aspect and all other aspects 10 4 - 35 , 4 - 30 , 4 - 25 , 4 - 20 , 4 - 15 , 4 - 12 , 4 - 11 , 4 - 10 , 4 - 9 , 4 - 8 , 4 - 6 , provided herein , the composition comprises at least seven 35 - 40 , 30 - 40 , 25 -40 , 20 -40 , 15 - 40 , 12 -40 , 11 -40 , 10 -40 , strains of viable , anaerobic , culturable gut bacteria selected 6 -40 , 5 - 40 , 10 - 20 , 10 - 30 , 10 - 25 , 15 -40 , 15 - 35 , 15 -30 , 15 -25 , from the group consisting of: Clostridium ramosum , 15 - 20 , 20 - 35 , 20 - 30 , 20 - 25 , 30 - 35 strains of viable , anaero Clostridium scindens, Clostridium hiranonsis , Clostridium bic , culturable gut bacteria . bifermentans, Clostridium leptum , Clostridium sardiniensis , 155 In another embodiment of this aspect and all other aspects Bacteroides fragilis . Bacteroides thetaiotaomicron . Bacte provided herein , the strains of viable , anaerobic , culturable roides ovatus . Parabacteroides goldsteinii , Prevotella tan - gut bacteria are selected from the group consisting of : ( 1 ) nerae, Clostridum hathewayi, Clostridum nexile , Clostridium ramosum , C . scindens, C . hiranonsis, C . bifer Clostridium hylemonae, Clostridium glycyrrhizinilyticum , mentans, C . leptum , and C . sardiniensis , or (ii ) Bacteroides Clostridium scindens, Clostridium lavalense , Clostridum 20 fragilis, B. thetaiotaomicron , B . ovatus, Parabacteroides fimetarium , Clostridium symbiosum , Clostridium spo - goldsteinii, and Prevotella tannerae. rosphaeroides, Dialister proprionicfaceins , Dialister succi In another embodiment of this aspect and all other aspects natiphilus, Parabacteroides distasonis , Parabacteroides provided herein , the composition comprises viable , anaero goldsteinii, Parabacteroides merdae, Peptostreptococcus bic , culturable gut bacteria including each of Clostridium anaerobius, Subdoligranulum variabile , and Veilonella ratti. 25 ramosum , C . scindens, C . hiranonsis , C . bifermentans , C . In another embodiment of this aspect and all other aspects leptum and C . sardiniensis . provided herein , the composition comprises at least eight In another embodiment of this aspect and all other aspects strains of viable , anaerobic , culturable gut bacteria selected provided herein , the composition comprises viable, anaero from the group consisting of: Clostridium ramosum , Clostridium scindens, Clostridium hiranonsis , Clostridium 30 bic , culturable gut bacteria including each of, Bacteroides bifermentans, Clostridium leptum , Clostridium sardiniensis , fragilis , B . thetaiotaomicron , B . ovatus , Parabacteroides Bacteroides fragilis, Bacteroides thetaiotaomicron , Bacte goldsteinii , and Prevotella tannerae. roides ovatus, Parabacteroides goldsteinii , Prevotella tan In another embodiment of this aspect and all other aspects nerae, Clostridum hathewayi, Clostridum nexile , provided herein , the composition comprises viable , anaero Clostridium hylemonae, Clostridium glycyrrhizinilyticum , 35. bic , culturable gut bacteria including each of Clostridium Clostridium scindens , Clostridium lavalense , Clostridum ramosum , C . scindens, C . hiranonsis , C . bifermentans, C . fimetarium , Clostridium symbiosum , Clostridium spo leptum , C . sardiniensis , Bacteroides fragilis, B . thetaiotao rosphaeroides, Dialister proprionicfaceins , Dialister succi micron , B . ovatus, Parabacteroides goldsteinii , and Pre natiphilus, Parabacteroides distasonis . Parabacteroides votella tannerae . goldsteinii , Parabacteroides merdae , Peptostreptococcus 40 Another aspect described herein relates to a pharmaceu anaerobius, Subdoligranulum variabile , and Veilonella ratti. tical composition comprising : at least four strains of viable , In another embodiment of this aspect and all other aspects anaerobic , culturable gut bacteria comprising : at least one provided herein , the composition comprises at least nine bacterial strain comprising a 16S rDNA sequence at least strains of viable , anaerobic , culturable gut bacteria selected 97 % identical to a 16S rDNA sequence present in a reference from the group consisting of: Clostridium ramosum , 45 strain operational taxonomic unit , the reference strain Clostridium scindens, Clostridium hiranonsis , Clostridium selected from the group consisting of: Clostridium ramo bifermentans, Clostridium leptum , Clostridium sardiniensis , sum , C . scindens , C . hiranonsis, C . bifermentans , C . leptum , Bacteroides fragilis, Bacteroides thetaiotaomicron , Bacte and C . sardiniensis ; or at least one bacterial strain compris roides ovatus , Parabacteroides goldsteinii , Prevotella tan - ing a 16S rDNA sequence at least 97 % identical to a 16S nerae , Clostridum hathewayi, Clostridum nexile , 50 rDNA sequence present in a reference strain operational Clostridium hylemonae , Clostridium glycyrrhizinilyticum , taxonomic unit , the reference strain selected from the group Clostridium scindens, Clostridium lavalense , Clostridum consisting of: Bacteroides fragilis , B . thetaiotaomicron , B . fimetarium , Clostridium symbiosum , Clostridium spo ovatus, Parabacteroides goldsteinii, and Prevotella tan rosphaeroides, Dialister proprionicfaceins , Dialister succi- nerae ; wherein the at least four strains of viable , anaerobic , natiphilus, Parabacteroides distasonis , Parabacteroides 55 culturable gut bacteria are present in an amount sufficient to goldsteinii, Parabacteroides merdae, Peptostreptococcus treat or prevent a food allergy when administered to an anaerobius, Subdoligranulum variabile , and Veilonella ratti. individual in need thereof; and a pharmaceutically accept In another embodiment of this aspect and all other aspects able carrier . provided herein , the composition comprises at least ten In another embodiment of this aspect and all other aspects strains of viable , anaerobic , culturable gut bacteria selected 60 provided herein , the composition comprises not more than from the group consisting of: Clostridium ramosum , forty strains of viable , anaerobic, culturable gut bacteria . Clostridium scindens, Clostridium hiranonsis , Clostridium In another embodiment of this aspect and all other aspects bifermentans, Clostridium leptum , Clostridium sardiniensis , provided herein , the composition comprises not more than Bacteroides fragilis , Bacteroides thetaiotaomicron , Bacte - thirty strains of viable , anaerobic , culturable gut bacteria . roides ovatus, Parabacteroides goldsteinii , Prevotella tan - 65 In another embodiment of this aspect and all other aspects nerae , Clostridum hathewayi, Clostridum nexile , provided herein , the composition comprises not more than Clostridium hylemonae , Clostridium glycyrrhizinilyticum , twenty strains of viable, anaerobic , culturable gut bacteria . US 10 , 265 , 349 B2 10 In another embodiment of this aspect and all other aspects strain (or strains ) that produces compounds capable of provided herein , the composition comprises not more than stimulating the aryl hydrocarbon receptor ( AhR ) receptor fifteen strains of viable , anaerobic , culturable gut bacteria . pathway in gut epithelial cells , antigen presenting cells In another embodiment of this aspect and all other aspects and / or T cells to stimulate development of regulatory T cell provided herein , the composition comprises not more than 5 responses ; ( v ) a preparation of a viable , culturable , anaero eleven strains of viable , anaerobic, culturable gut bacteria . bic gut bacterial strain (or strains ) that produces compounds In another embodiment of this aspect and all other aspects capable of stimulating the pregnane X receptor with ben provided herein , the composition comprises at least five eficial effects upon gut barrier function and / or development strains of viable , anaerobic , culturable gut bacteria . of regulatory T cell responses ; ( vi) a preparation of a viable , In another embodiment of this aspect and all other aspects 10 culturable , anaerobic gut bacterial strain ( or strains ) that provided herein , the composition comprises at least six produces compounds capable of stimulating the ROR strains of viable , anaerobic , culturable gut bacteria . gamma (RAR -related orphan receptor gamma ) pathways to In another embodiment of this aspect and all other aspects stimulate development of regulatory T cell responses via provided herein , the composition comprises at least seven direct stimulation or RORgamma -activated pathways in gut strains of viable , anaerobic , culturable gut bacteria . 15 antigen presenting cells and / or epithelial cells that then In another embodiment of this aspect and all other aspects stimulate regulatory T cell responses ; (vii ) a preparation of provided herein , the composition comprises at least eight a viable , culturable , anaerobic gut bacterial strain ( or strains ) strains of viable, anaerobic , culturable gut bacteria . that stimulates host production of mucins and complex In another embodiment of this aspect and all other aspects glycoconjugates that improve gut barrier function and colo provided herein , the composition comprises at least nine 20 nization by protective commensal species ; ( viii ) a prepara strains of viable, anaerobic , culturable gut bacteria . tion of a viable , culturable , anaerobic gut bacterial strain ( or In another embodiment of this aspect and all other aspects strains) that alters the gut luminal environment to reduce the provided herein , the composition comprises at least ten deleterious activities of dysbiotic species promoting devel strains of viable , anaerobic , culturable gut bacteria . opment of unhealthy allergic T cell responses to food In another embodiment of this aspect and all other aspects 25 antigens; ( ix ) a preparation of a viable , culturable , anaerobic provided herein , the composition comprises eleven strains of gut bacterial strain ( or strains ) that alters the gut luminal viable , anaerobic , culturable gut bacteria. environment to promote improved colonization by other In another embodiment of this aspect and all other aspects members of the administered consortium for any of the provided herein , the microbial strains do not comprise any above stated effects , and / or colonization by existing benefi of the Species Escherichia coli , Klebsiella pneumoniae , 30 cial species in the patients underlying microbiota ; and ( x ) a Proteus mirabilis , Enterobacter cloacae , Bilophila wads - preparation of a viable , culturable , anaerobic gut bacterial worthia , Alistipes onderdonkii , Desulfovibrio species , Lac - strain (or strains ) that promotes the colonization or growth tobacillus johnsoni, and Parasutterella excrementihominis . of a bacterial strain in a preparation of ( i) - (ix ) above , in vivo ; In another embodiment of this aspect and all other aspects and wherein the composition comprises no more than forty provided herein , the microbial strains do not comprise 35 microbial species . bacteria of the Genera Bilophila , Enterobacter, Escherichia , In one embodiment of this aspect and all other aspects Klebsiella , Proteus, Alistipes, Blautia , Desulfovibrio , or provided herein , the composition comprises no more than Parasutterella . thirty microbial species. In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the microbial strains do not comprise 40 provided herein , the composition comprises no more than bacteria of the Families Desulfovibrionaceae , Enterobacte - twenty microbial species . riaceae , Rikenellaceae , and Sutterellaceae . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition comprises no more than provided herein , the microbial strains do not comprise fifteen microbial species . bacteria of the Families Lactobacillaceae , or Enterbacteri - 45 In another embodiment of this aspect and all other aspects aceae provided herein , the composition comprises no more than In another embodiment of this aspect and all other aspects eleven microbial species . provided herein , the microbial strains do not comprise In another embodiment of this aspect and all other aspects bacteria of the Order Burkholdales , Desulfovibrionales , or provided herein , the composition comprises at least five of Enterobacteriales . 50 the preparations ( 1 ) - ( x ) . Another aspect provided herein relates to a pharmaceuti - In another embodiment of this aspect and all other aspects cal composition comprising a microbial consortium of cul provided herein , the composition comprises at least six of turable species, and a pharmaceutically acceptable carrier, the preparations ( i) - ( x ) . wherein the composition comprises at least four preparations In another embodiment of this aspect and all other aspects selected from the group consisting of: ( i ) a preparation of a 55 provided herein , the composition comprises at least seven of viable , culturable , anaerobic gut bacterial strain (or strains ) the preparations ( i ) - ( x ) . that expresses exopolysaccharide, lipoteichoic acid (LTA ) , In another embodimentof this aspect and all other aspects lipopolysaccharide ( LPS ) or other microbial adjuvant mol- provided herein , the composition comprises at least eight of ecules that promote the development of regulatory T cells the preparations ( i ) - ( x ) . ( Treg ) ; ( ii ) a preparation of a viable , culturable , anaerobic 60 In another embodiment of this aspect and all other aspects gut bacterial strain ( or strains ) that produces butyrate and /or provided herein , the composition comprises at least nine of propionate fermentation products via fermentation of car - the preparations ( 1 ) - ( x ). bohydrates and other carbon sources in the gut lumen ; ( iii ) In another embodiment of this aspect and all other aspects a preparation of one or more viable , culturable , anaerobic provided herein , the composition comprises each of the gut bacterial strains that alone or in combination performs 65 preparations ( i ) - ( x ) . the full complement of bile acid transformations ; ( iv ) a In another embodiment of this aspect and all other aspects preparation of a viable , culturable , anaerobic gut bacterial provided herein , the anaerobic gut bacterial strain that US 10 , 265 , 349 B2 11 12 expresses exopolysaccharide that promotes the development Bacteroides spp . In another embodiment of this aspect and of regulatory T cells ( Treg ) is selected from the group all other aspects provided herein , the dysbiotic species consisting of: Eubacterium rectale , Clostridium ramosum , comprises a species in the Families Enterobacteriaceae or Butyrovibrio crossatus, Roseburia intestinalis , Clostridium Desulfonovibriacaea . scindens, Clostridium hylemonae , Hungatella hathawayi, 5 In another embodiment of this aspect and all other aspects Clostridium symbiosum , Faecalibacterium prausnitzii , Sub - provided herein , the anaerobic gut bacterial strains alter the doligranulum variabile , Bacteroides thetaiotaomicron , gut luminal environment to promote improved colonization Bacteroides fragilis, Bacteroides ovatus, Parabacetroides by othermembers of the administered consortium for any of goldsteinii , Parabacteroides merdae , Parabacteroides dis the above stated effects , and /or colonization by existing tasonis , and Prevotella tannerae . 10 In another embodiment of this aspect and all other aspects beneficial species in the patients underlying microbiota is provided herein , the anaerobic gut bacterial strain that strain Bacteroides thetaiotaomicron , Bacteroides fragilis , or that produces butyrate , propionate and /or succinate fermen Bacteroides spp . In another embodiment of this aspect and tation products via fermentation of carbohydrates in the gut all other aspects provided herein , the beneficial species lumen is selected from the group consisting of: Bacteroides 15 comprises non - pathogenic Clostridia spp . and other non fragilis , Bacteroides thetaiotaomicron , Bacteroides ovatus, pathogenic commensal strains . Clostridium sardiniensis. Clostridium hiranonsis. Faceali- In another embodiment of this aspect and all other aspects bacterium prausnitzii, Butyrovibrio spp ., Eubacterium rec - provided herein , the pharmaceutically acceptable carrier tale , and Roseburia intestinalis . comprises an enteric coating composition that encapsulates In another embodiment of this aspect and all other aspects 20 the anaerobic gut bacterial strains. provided herein , the anaerobic gut bacterial strain that alone In another embodiment of this aspect and all other aspects or in combination performs the full complement of bile acid provided herein , the composition is formulated to deliver the transformations lumen is selected from the group consisting viable bacteria to the small intestine. of: Bacteroides fragilis , Bacteroides thetaiotaomicron , In another embodiment of this aspect and all other aspects Bacteroides ovatus, Clostridium sardiniensis, Clostridium 25 provided herein , wherein the enteric -coating composition is hiranonsis , Face?libacterium prausnitzii, Butyrovibrio spp ., in the form of a capsule , gel, pastille , tablet or pill. Eubacterium rectale , and Roseburia intestinalis . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the strains of viable , anaerobic gut bacteria provided herein , the anaerobic gut bacterial strain that are human anaerobic gut bacteria . produces aryl hydrocarbon receptor agonists sufficient to 30 In another embodiment of this aspect and all other aspects stimulate host aryl hydrocarbon receptor pathways com - provided herein , the strains of viable anaerobic gut bacteria prises at least one gene associated with the synthesis of are selected from the group consisting of: Clostridium tryptophan , tyrosine or the synthesis of quinone molecules ramosum , Clostridium scindens, Clostridium hiranonsis , In another embodiment of this aspect and all other aspects Clostridium bifermentans, Clostridium leptum , Clostridium provided herein , the anaerobic gut bacterial strain that 35 sardiniensis , Bacteroides fragilis, Bacteroides thetaiotaomi promotes the colonization or growth of a bacterial strain in cron , Bacteroides ovatus , Parabacteroides goldsteinii, Pre a preparation recited in claim 2 is Bacteroides thetaiotao votella tannerae , Clostridum hathewayi , Clostridum nexile , micron , or Bacteroides fragilis . Clostridium hylemonae, Clostridium glycyrrhizinilyticum , In another embodiment of this aspect and all other aspects Clostridium scindens, Clostridium lavalense, Clostridum provided herein , the anaerobic gut bacterial strain that 40 fimetarium , Clostridium symbiosum , Clostridium spo produces compounds endogenously or by metabolizing rosphaeroides , Dialister proprionicfaceins, Dialister succi ingested precursors , that is capable of stimulating the preg n atiphilus, Parabacteroides distasonis , Parabacteroides nane X receptor with beneficial effects upon gut barrier goldsteinii, Parabacteroides merdae, Peptostreptococcus function and /or development of regulatory T cell responses anaerobius, Subdoligranulum variabile , and Veilonella ratti . is a strain that expresses desmolase and/ or hydroxysteroid 45 In another embodiment of this aspect and all other aspects dehydrogenase . provided herein , the strains of viable anaerobic gut bacteria In another embodiment of this aspect and all other aspects are selected from the group consisting of: Clostridium provided herein , the anaerobic gut bacterial strain that ramosum , C . scindens, C . hiranonsis , C . bifermentans, C . produces compounds endogenously or by metabolizing leptum , C . sardiniensis, Bacteroides fragilis , B . thetaiotao ingested precursors , that is capable of stimulating the ROR - 50 micron , B . ovatus , Parabacteroides goldsteinii , and Pre gamma (RAR - related orphan receptor gamma ) pathways to votella tannerae. stimulate development of regulatory T cell responses is a In another embodiment of this aspect and all other aspects strain that expresses at least one cholesterol reductase or provided herein , the strains of viable anaerobic gut bacteria another enzyme( s) capable of metabolizing sterol com are selected from the group consisting of: (i ) Clostridium pounds. 55 ramosum , C . scindens, C . hiranonsis , C . bifermentans, C . In another embodiment of this aspect and all other aspects leptum , and C . sardiniensis , or ( ii ) Bacteroides fragilis , B . provided herein , the anaerobic gut bacterial strain that is thetaiotaomicron , B . ovatus, Parabacteroides goldsteinii, capable of stimulating host mucins and complex glycocon - and Prevotella tannerae . jugates that improve gut barrier function and colonization by In another embodiment of this aspect and all other aspects protective commensal species is Bacteroides thetaiotaomi- 60 provided herein , the strains of viable anaerobic gut bacteria cron or Bacteroides fragilis. consist essentially of Clostridium ramosum , C . scindens, C . In another embodiment of this aspect and all other aspects hiranonsis , C . bifermentans, C . leptum , and C . sardiniensis . provided herein , the anaerobic gutbacterial strains that alter In another embodiment of this aspect and all other aspects the gut luminal environment to reduce the deleterious activi - provided herein , the strains of viable anaerobic gut bacteria ties of dysbiotic species that contribute to development of 65 consist essentially of Bacteroides fragilis , B . thetaiotaomi pathogenic allergic T cell responses to food antigens is cron , B . ovatus, Parabacteroides goldsteinii , and Prevotella Bacteroides thetaiotaomicron , Bacteroides fragilis , or tannerae . US 10 , 265 , 349 B2 13 14 In another embodiment of this aspect and all other aspects C . sardiniensis, Bacteroides fragilis, B . thetaiotaomicron , B . provided herein , the strains of viable anaerobic gut bacteria ovatus , Parabacteroides goldsteinii, and Prevotella tan consist essentially of Clostridium ramosum , C . scindens, C . nerae . hiranonsis , C . bifermentans, C . leptum , C . sardiniensis , In another embodiment of this aspect and all other aspects Bacteroides fragilis , B . thetaiotaomicron , B . ovatus, Para - 5 provided herein , the strains of gut bacteria administered are bacteroides goldsteinii , and Prevotella tannerae . selected from the group consisting of: ( i ) Clostridium ramo In another embodiment of this aspect and all other aspects sum , C . scindens, C . hiranonsis , C . bifermentans , C . leptum , provided herein , the strains of viable anaerobic gut bacteria and C . sardiniensis , or ( ii ) Bacteroides fragilis , B . thetaio are present in substantially equal biomass. taomicron , B . ovatus, Parabacteroides goldsteinii , and Pre 10 votella tannerae . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition is formulated to deliver a provided herein , the composition is administered by oral dose of at least 1x10° colony forming units (CFUS ) . administration , enema, suppository , or orogastric tube . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition is formulated to deliver at 15 provided herein , the minimal microbial consortium or least 1x10° CFUs in less than 30 capsules per one time dose . viable, culturable , anaerobic gut bacterial strain ( s ) is / are In another embodiment of this aspect and all other aspects isolated and /or purified from a subject known to be tolerant provided herein , the composition is frozen for storage . to a selected food allergen . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the strains of viable anaerobic gut bacteria 20 provided herein , the strains of gut bacteria are cultured under are encapsulated under anaerobic conditions . In another anaerobic conditions. embodiment of this aspect and all other aspects provided In another embodiment of this aspect and all other aspects herein , the strains of viable anaerobic gut bacteria are provided herein , the anaerobic conditions comprise one or lyophilized under anaerobic conditions . more of the following : (i ) oxygen impermeable capsules, ( ii ) In another embodiment of this aspect and all other aspects 25 addition of N - acetylcysteine , cysteine , methylene blue , or a provided herein , wherein anaerobic conditions comprise one reducing factor to the composition , or ( iii ) use of spores for or more of the following : ( i ) oxygen impermeable capsules , organisms that sporulate. ( ii ) addition of N - acetylcysteine, cysteine or methylene blue In another embodiment of this aspect and all other aspects to the composition , ( iii ) use of spores for organisms that provided herein , the composition administered further com sporulate , and ( iv ) addition of a reducing factor to the 3030 prises a pre -biotic composition . composition . In another embodiment of this aspect and all other aspects provided herein , the composition is enteric -coated . In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the enteric -coating comprises a polymer , provided herein , the treatment administered prevents and /or nanoparticle , fatty acid , shellac, or a plant fiber. 35 reverses TH2 programming of Tregs and other mucosal T In another embodiment of this aspect and all other aspects cell populations. provided herein , the composition further comprises a pre In another embodiment of this aspect and all other aspects biotic composition . provided herein , the subject is a human subject. In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the composition is encapsulated , a recon - 40 provided herein , the method further comprises a step of stituted lyophilisate , a food item , or is formulated as a liquid , diagnosing the subject as likely to develop a food allergy . gel , fluid - gel, or nanoparticles in a liquid . In another embodiment of this aspect and all other aspects Another aspect described herein relates to a method for provided herein , the method further comprising a step of preventing the onset of a food allergy in a subject, the testing a fecal sample from the subject for the presence method comprising : administering to a subject a composi- 45 and /or levels of the bacteria in the minimal microbial tion as described herein , thereby preventing the onset of a consortium or the viable , culturable , anaerobic gut bacterial food allergy in the subject . strain (s ) . In one embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the at least 4 strains of gut bacteria admin provided herein , the food allergy comprises allergy to soy , istered are selected from the group consisting of : 50 wheat, eggs, dairy, peanuts, tree nuts , shellfish , fish , mush Clostridium ramosum , Clostridium scindens, Clostridium rooms, stone fruits and other fruits . hiranonsis , Clostridium bifermentans , Clostridium leptum , In another embodiment of this aspect and all other aspects Clostridium sardiniensis , Bacteroides fragilis , Bacteroides provided herein , the composition is administered before the thetaiotaomicron , Bacteroides ovatus, Parabacteroides first exposure to a potential food allergen . goldsteinii , Prevotella tannerae , Clostridum hathewayi, 55 In another embodiment of this aspect and all other aspects Clostridum nexile , Clostridium hylemonae , Clostridium gly - provided herein , the composition is administered upon clini cyrrhizinilyticum , Clostridium scindens, Clostridium laval- cal signs of atopic symptoms. ense , Clostridum fimetarium , Clostridium symbiosum , In another embodiment of this aspect and all other aspects Clostridium sporosphaeroides, Dialister proprionicfaceins, provided herein , the composition is administered to indi Dialister succinatiphilus, Parabacteroides distasonis , Para - 60 viduals with diagnosed food allergy bacteroides goldsteinii , Parabacteroides merdae, Pepto - In another embodiment of this aspect and all other aspects streptococcus anaerobius, Subdoligranulum variabile , and provided herein , the subject is pretreated with an antibiotic . Veilonella ratti. In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the subject is not pretreated with an anti provided herein , the strains of gut bacteria administered are 65 biotic . selected from the group consisting of: Clostridium ramo - Another aspect described herein relates to a method for sum , C . scindens, C . hiranonsis , C . bifermentans, C . leptum , reducing or eliminating a subject' s immune reaction to a US 10 , 265 , 349 B2 15 16 food antigen , the method comprising : administering to a testing a fecal sample from the subject for the presence subject a composition as described herein , thereby reducing and /or levels of the bacteria in the minimal microbial or eliminating a subject ' s immune reaction to a food aller consortium or viable , culturable , anaerobic gut bacterial gen . strain ( s ) . In one embodiment of this aspect and all other aspects 5 In another embodiment of this aspect and all other aspects provided herein , the strains of bacteria administered are provided herein , the food allergy comprises allergy to soy , selected from the group consisting of: Clostridium ramo wheat , eggs, dairy, peanuts , tree nuts , shellfish , fish , mush sum , Clostridium scindens, Clostridium hiranonsis , rooms, stone fruits or other fruits . Clostridium bifermentans, Clostridium leptum , Clostridium In another embodiment of this aspect and all other aspects sardiniensis , Bacteroides fragilis , Bacteroides thetaiotaomi- 10 provided herein , the composition is administered after an cron , Bacteroides ovatus, Parabacteroides goldsteinii , Pre - initial exposure and /or reaction to a potential food allergen . votella tannerae, Clostridum hathewayi, Clostridum nexile , In another embodiment of this aspect and all other aspects Clostridium hylemonae , Clostridium glycyrrhizinilyticum , provided herein , the biomass of each of the microbes in the Clostridium scindens, Clostridium lavalense, Clostridum administered compositions is greater than the biomass of fimetarium , Clostridium symbiosum , Clostridium spo - 15 each of the microbes relative to a reference . rosphaeroides, Dialister proprionicfaceins , Dialister succi - In another embodiment of this aspect and all other aspects natiphilus, Parabacteroides distasonis , Parabacteroides provided herein , the subject is pretreated with an antibiotic . goldsteinii , Parabacteroides merdae , Peptostreptococcus In another embodiment of this aspect and all other aspects anaerobius, Subdoligranulum variabile , and Veilonella ratti. provided herein , the subject is not pretreated with an anti In another embodiment of this aspect and all other aspects 20 biotic . provided herein , the strains of viable gut bacteria are In another embodiment of this aspect and all other aspects selected from the group consisting of: Clostridium ramo provided herein , the subject is pretreated with a fasting sum , C . scindens, C . hiranonsis, C . bifermentans, C . leptum , period not longer than 24 hours. C . sardiniensis, Bacteroides fragilis , B . thetaiotaomicron , B . Another aspect provided herein relates to a method of ovatus , Parabacteroides goldsteinii , and Prevotella tan - 25 monitoring a subject ' s microbiome, the method comprising : nerae . determining the presence and / or biomass of at least one In another embodiment of this aspect and all other aspects member of a minimal microbial consortium in a biological provided herein , the strains of viable gut bacteria are sample obtained from a subject, and wherein if the at least selected from the group consisting of: ( i ) Clostridium ramo - one member is absent or the biomass of the at least one sum , C . scindens, C . hiranonsis, C . bifermentans, C . leptum , 30 member is low relative to a reference , the subject is treated and C . sardiniensis , or ( ii ) Bacteroides fragilis , B . thetaio - with the composition as described herein . taomicron , B . ovatus, Parabacteroides goldsteinii , and Pre - In another embodiment of this aspect and all other aspects votella tannerae . provided herein , the method further comprises predicting In another embodiment of this aspect and all other aspects that a subject will have an immune response to a food provided herein , the composition is administered by oral 35 allergen when the at least one member is absent, the biomass administration , enema , suppository , or orogastric tube . of the at least one member is low relative to a reference , or In another embodiment of this aspect and all other aspects at least one member of a dysbiotic species is present, or is provided herein , the minimal microbial consortium or the elevated relative to a reference . viable , culturable , anaerobic gut bacterial strain ( s ) is / are In another embodiment of this aspect and all other aspects isolated and /or purified from a subject known to be tolerant 40 provided herein , the method is repeated at least one addi to a selected food allergen . tional time. In another embodiment of this aspect and all other aspects In another embodiment of this aspect and all other aspects provided herein , the strains of bacteria or minimal microbial provided herein , the biological sample is a fecal sample . consortium is cultured and /or maintained under anaerobic Another aspect described herein relates to a synergistic conditions . 45 microbial composition comprising: ( a ) a first microbial In another embodiment of this aspect and all other aspects consortium consisting essentially of four to six strains of provided herein , anaerobic conditions comprise one or more viable, non -pathogenic gut bacteria , wherein the strains of of the following : ( i ) oxygen impermeable capsules , ( ii ) viable non - pathogenic gut bacteria are selected from the addition of N -acetylcysteine , cysteine, methylene blue or a group consisting of: Clostridium ramosum , C . scindens , C . reducing factor to the composition , or ( iii ) use of spores for 50 hiranonsis , C . bifermentans , C . leptum , and C . sardiniensis , organisms that sporulate . and ( b ) a second microbial consortium consisting essentially In another embodiment of this aspect and all other aspects of four to five strains of viable, non -pathogenic gut bacteria , provided herein , the composition administered further com wherein the strains of viable non - pathogenic gut bacteria are prises a pre -biotic composition . selected from the group consisting of: Bacteroides fragilis , In another embodiment ofthis aspect and all other aspects 55 B . thetaiotaomicron , B . ovatus, Parabacteroides goldsteinii , provided herein , the composition is enteric - coated . and Prevotella tannerae , wherein one or more members of In another embodiment of this aspect and all other aspects the second microbial consortium increases the colonization provided herein , the treatment prevents and/ or reverses TH2 and /or persistence of one or more members of the first programming of Tregs. microbial consortium in a mammalian host . In another embodiment of this aspect and all other aspects 60 provided herein , the subject is a human subject. BRIEF DESCRIPTION OF THE FIGURES In another embodiment of this aspect and all other aspects provided herein , the method further comprises a step of FIG . 1 . Tolerance failure in food allergy . Food allergy is diagnosing the subject as having an IgE -mediated food a failure of oral tolerance to food antigens associated with allergy. 65 Th2 immunity and allergen - specific IgE responses . In another embodiment of this aspect and all other aspects FIG . 2 . Experimental model : 114raF709 mutant mice . provided herein , the method further comprises a step of FIG . 3 . An exemplary ovalbumin sensitization protocol. US 10 , 265 , 349 B2 17 FIG . 4 . Ovalbumin (OVA ) - induced food allergic reaction OVA challenge and the following analyses: FIG . 23B , in 114raF709 mice . temperature changes after OVA challenge as a clinical FIG . 5 . Allergen -specific TR cell deficiency in allergic marker of anaphylaxis . FIG . 23C , Changes to total and 114raF709 mice . OVA -specific IgE titers. FIG . 23D , MMCP - 1 production FIG . 6 . Oral allergic sensitization in F709 mutantmice is 5 ( indicative of mast cell degranulation ). FIGS. 23E & 23F , associated with dysbiosis . FAEffect of consortia on development of mucosal Foxp3 + FIG . 7 . An exemplary protocol to test if microbiota of CD4 + T cells . FIGS. 23G & 23H , Effects on IL - 4 and sensitized 114raF709 mice transmit susceptibility to food interferon gamma (IFNY ) production in mucosal CD4 + T allergy . cells . FIG . 8 . The microbiota of 114raF709 mice promotes 10 FIG . 24A -FIG . 24L . GP- II consortia ( Bacteriodetes) pro allergic sensitization and anaphylaxis in germ free mice . tects against food allergy without prior antibiotic knock FIG . 9 . The microbiota of Il4raF709 mice promotes down of the flora . allergic sensitization and anaphylaxis . FIG . 25A - FIG . 251. GP - I consortia (Clostridiales ) can FIG . 10 . An exemplary protocol to determine if micro - cure food allergy without the use of antibiotics in conven biota of food tolerant mice transmits protection against food 15 tional mice . FIG . 25A , Conventional wild - type or allergy. IL 4raF709 mice were challenged weekly with OVA for 8 FIG . 11A -FIG . 11D . The microbiota of food tolerantmice weeks, after which they received 5x108 CFU of the GP - I protect against allergic sensitization and anaphylaxis in a consortium 8 times over 4 weeks prior to final OVA chal genetically susceptible host . lenge . Mice received no prior antibiotic knockdown of the FIG . 12A -FIG . 12D . The microbiota of food tolerant mice 20 underlying microbiota prior to GP - I administration . FIG . promotes the formation of allergen -specific Treg cells. 25B , Temperature changes with final OVA challenge . FIG . FIG . 13 . A graphical visualization of relative abundances 25C , Changes in total and OVA - specific IgE titers . FIG . of phyla : 8 weeks ovalbumin (OVA ) treatment. 25D , Changes in percentages of mucosal T cells , Foxp3 FIG . 14 . Selected OTUs showing differences between WT regulatory T cells . FIG . 25E , IL4 + mucosal cells and regu and F709 mice : OVA , duodenum , jejunum , ileum . 25 latory T cells . FIGS . 25F & 25G , Changes in CD4 + IL - 17 FIG . 15 . An exemplary protocol for testing whether production in wild - type and IL4raF709 mice receiving PBS treatment with defined bacterial mixes will protect against or GP - I consortia . FIGS . 25H & 251, Changes in IL - 17 food allergy . production of Foxp3 + regulatory cells . FIG . 16A -FIG . 16D . Clostridia and Bacteriodetes protect against development of allergen - specific responses and ana - 30 DETAILED DESCRIPTION phylaxis . FIG . 17 . Oral allergic sensitization is associated with TR Definitions cell TH2 reprogramming . As used herein , the term " food allergy ” refers to a failure FIG . 18A - FIG . 18F . Deletion of 114 / 1113 in T , cells of oral tolerance to food antigens associated with Th2 protects against food allergy. 35 immunity and allergen -specific IgE responses . That is , an FIG . 19. Reduced TH2 - skewed Treg phenotype indicating immune response is generated in response to particular food that Clostridia and Bacteriodetes have two differentmolecu - antigens and can lead to hives, gastrointestinal symptoms, lar mechanisms of action . abdominal pain , anaphylaxis and even death . FIG . 20A - FIG . 20C . Short chain fatty acid (SCFA ) As used herein , the term “ microbiota ” can refer to the therapy does not rescue food allergy in 114raF709 mice . 40 human microbiome, the human microbiota , or the human gut FIG . 21A - FIG . 211. Gut protect (GP ) - I and GP - II are microbiota . The human microbiome (or human microbiota ) effective in treat - to - prevent food allergy in conventional may be understood as the aggregate of microorganisms that wild -type and IL4RA F709 mice . FIG . 21A , Conventional reside on the surface and in deep layers of skin , in the saliva IL4raF709 mice are pre - treated with oral broad -spectrum and oralmucosa , in the conjunctiva , and in the genitourinary antibiotics 1 week prior to initiating OVA sensitization .Mice 45 and gastrointestinal tracts of humans . The human microbi receive weekly doses of 5x108 CFU of the aggregate con - ome is comprised of bacteria , fungi, viruses , and archaea . At sortia of either GP -1 , GP - II or NCC before oral OVA least some of these organisms perform tasks that are useful challenge . Mice receive the final OVA challenge at 8 weeks, for the human host . Under normal circumstances, these after which temperature drop (FIG . 21B ), from anaphylaxis , microorganisms do not cause acute disease to the human impact to IgE titers ( FIG . 21C ) , mast cell protease - 1 ( FIG . 50 host, but instead cause no harm or participate in maintaining 21D ) , mast cell recruitment to the small bowel (FIG . 21E ) , health . Hence , this population of organisms is frequently development of Foxp3 + regulatory T cells (FIG . 21F ) , and referred to as the “ normal flora . ” The population of micro total numbers (FIG . 21G ), and interferon gamma vs. IL - 4 organisms living in the human gastrointestinal tract is com producing T cells (FIGS . 21H & 211) , are measured . monly referred to as “microbial flora” , “ gut flora” , and /or FIG . 22A - FIG . 22H . GP - 1 ( Clostridiales ) and GP - II 55 " gut microbiota ” . The microbial flora of the human gut ( Bacteroidetes ) consortia protect germ - free mice in treat- to - encompasses a wide variety of microorganisms that aid in prevent regimens . Gnotobiotic mice inoculated with either digestion , the synthesis of vitamins and other metabolites, the GP - I or GP - II consortia (one time) prior to OVA sensi- and creating enzymes not produced by the human body. tization ( left arrow , FIG . 22A ) and final challenge ( right As used herein , the term “ minimalmicrobial consortium ” arrow , FIG . 22A ). 60 refers to a mixed population of cells comprising at least two FIG . 23A - FIG . 23H . GP -I and GP- II consortia cure food species of gut bacteria that do not promote acute disease in allergy in conventional IL4raF709 mice while negative a subject. The microbial consortium is “ minimal” when an control consortia (NCC ) does not. FIG . 23A , Conventional additional bacterial species is added and there is no addi IL4raF709 mice are sensitized to OVA for 8 weeks and then tional benefit ( e . g . , less than 5 % ) in avoiding or mitigating given oral antibiotics prior to challenge over 4 weeks with 65 an allergic response . In some embodiments , the minimal the GP - I (Clostridiales ) , GP - II (Bacteroidetes ) or NCC microbial consortium comprises at least 3 , at least 4 , at least ( Proteobacteria ) consortia . Afterward , mice receive a final 5 , at least 6 , at least 7 , at least 8 , at least 9, at least 10 , at least US 10 , 265 , 349 B2 19 20 11 , or more different species of bacteria . In some embodi- healthier . Dysbiosis may be due to a decrease in diversity , ments , the minimal microbial consortium comprises at least the overgrowth of one or more pathogens or pathobionts , one species of bacteria from the phyla Clostridia and/ or symbiotic organisms able to cause disease only when certain Bacteroidetes. genetic and /or environmental conditions are present in a “ Operational taxonomic unit (OTU , plural OTUS) ” refers 5 patient, or the shift to an ecological network that no longer to a terminal leaf in a phylogenetic tree and is defined by a provides a beneficial function to the host and therefore no specific genetic sequence and all sequences that share a longer promotes health . specified degree of sequence identity to this sequence at the The terms " patient” , “ subject” and “ individual” are used level of species . A “ type ” or a plurality of " types" of bacteria interchangeably herein , and refer to an animal, particularly includes an OTU or a plurality of different OTUS, and also 10 a human , to whom treatment , including prophylactic treat encompasses a strain , species , genus, family or order of ment is provided . The term “ subject ” as used herein refers to bacteria . The specific genetic sequence may be the 16S human and non -human animals . The term " non -human rRNA sequence or a portion of the 16S rRNA sequence, or animals” and “ non -human mammals ” are used interchange it may be a functionally conserved housekeeping gene found ably herein includes all vertebrates, e . g . , mammals , such as broadly across the eubacterial kingdom . OTUs generally 15 non - human primates , (particularly higher primates ), sheep , share at least 95 % , 96 % , 97 % , 98 % , or 99 % sequence dog , rodent ( e . g . mouse or rat) , guinea pig , goat , pig , cat, identity . OTUs are frequently defined by comparing rabbits , cows, and non -mammals such as chickens, amphib sequences between organisms. Sequences with less than the ians, reptiles etc . In one embodiment, the subject is human . specified sequence identity ( e. g . , less than 97 % ) are not in another embodiment, the subject is an experimental considered to form part of the same OTU . 20 animal or animal substitute as a disease model. In another " Clade” refers to the set of OTUs or members of a embodiment, the subject is a domesticated animal including phylogenetic tree downstream of a statistically valid node in companion animals ( e . g ., dogs, cats , rats , guinea pigs , ham a phylogenetic tree . The clade comprises a set of terminal sters etc . ) . leaves in the phylogenetic tree that is a distinct monophy As used herein , the term " enteric coated drug delivery letic evolutionary unit. 25 device” or “ enteric coated composition ” refers to any drug In microbiology, “ 16S sequencing ” or “ 16S rRNA ” or delivery method that can be administered orally but is not “ 16S -rRNA ” or “ 16S ” refers to sequence derived by char - degraded or activated until the device enters the intestines . acterizing the nucleotides that comprise the 16S ribosomal Such methods can utilize a coating or encapsulation that is RNA gene (s ). The bacterial 16S rDNA is approximately degraded using e . g . , pH dependent means , permitting pro 1500 nucleotides in length and is used in reconstructing the 30 tection of the delivery device and the microbial consortium evolutionary relationships and sequence similarity of one to be administered or transplanted throughout the upper bacterial isolate to a second isolate using phylogenetic gastrointestinal tract until the device reaches the alkaline pH approaches . 16S sequences are used for phylogenetic recon - of the intestines . In one embodiment, the enteric coated drug struction as they are in general highly conserved , but contain delivery device comprises a capsule or a pill . Such drug specific hypervariable regions that harbor sufficient nucleo - 35 delivery devices are known to those of skill in the art. tide diversity to differentiate genera and species of most As used herein , a “ prebiotic ” refers to an ingredient that bacteria , as well as fungi. allows or promotes specific changes , both in the composi The “ V1 -V9 regions ” of the 16S rRNA refers to the first tion and /or activity in the gastrointestinal microbiota that through ninth hypervariable regions of the 16S rRNA gene may ( or may not) confer benefits upon the host. In some that are used for genetic typing of bacterial samples . These 40 embodiments , a prebiotic can include one or more of the regions in bacteria are defined by nucleotides 69- 99 , 137 - following : fructooligosaccharide , galactooligosaccharides , 242, 433 -497 , 576 -682 , 822- 879 , 986 - 1043, 1117- 1173, hemicelluloses ( e. g. , arabinoxylan , xylan , xyloglucan , and 1243 - 1294 and 1435 - 1465 respectively using numbering glucomannan ) , inulin , chitin , lactulose , mannan oligosac based on the E . coli system of nomenclature . Brosius et al ., charides, oligofructose -enriched inulin , gums ( e . g ., guar Complete nucleotide sequence of a 16S ribosomal RNA 45 gum , gum arabic and carrageenan ), oligofructose , oligodex gene from Escherichia coli , PNAS 75 ( 10 ) : 4801 - 4805 trose , tagatose, resistant maltodextrins ( e . g ., resistant ( 1978 ). In some embodiments , at least one of the V1, V2 , starch ), transgalactooligosaccharide, pectins ( e . g . , xyloga V3 , V4 , V5 , V6 , 17 , 18, and V9 regions are used to lactouronan , citrus pectin , apple pectin , and rhamnogalac characterize an OTU . In one embodiment, the V1, V2 , and turonan - I ) , dietary fibers ( e . g ., soy fiber , sugarbeet fiber , pea V3 regions are used to characterize an OTU . In another 50 fiber, corn bran , and oat fiber) and xylooligosaccharides . embodiment, the V3 , V4 , and V5 regions are used to As used herein , the terms " administering , ” “ introducing ” characterize an OTU . In another embodiment, the V4 region and “ transplanting ” are used interchangeably in the context is used to characterize an OTU . A person of ordinary skill in of the placement of cells , e . g . a microbial consortium , as the art can identify the specific hypervariable regions of a described herein into a subject, by a method or route which candidate 16S rRNA by comparing the candidate sequence 55 results in at least partial localization of the introduced cells in question to the reference sequence and identifying the at a desired site , such as the intestines or a region thereof, hypervariable regions based on similarity to the reference such that a desired effect ( s ) is produced ( e . g . , tolerance to a hypervariable regions . food allergen ) . The cells can be administered by any appro “ Dysbiosis ” refers to a state of the microbiota or micro - priate route which results in delivery to a desired location in biome of the gut or other body area , including mucosal or 60 the subject where at least a portion of the delivered cells or skin surfaces in which the normal diversity and /or function components of the cells remain viable . The period of viabil of the ecological network is disrupted . Any disruption from ity of the cells after administration to a subject can be as the preferred ( e . g ., ideal) state of the microbiota can be short as a few hours , e . g ., twenty - four hours, to a few days , considered a dysbiosis , even if such dysbiosis does not result to as long as several years , i. e . , long - term engraftment. in a detectable decrease in health . This state of dysbiosis 65 As used herein “ preventing ” or “ prevention ” refers to any may be unhealthy , it may be unhealthy under only certain methodology where the disease state does not occur due to conditions , or it may prevent a subject from becoming the actions of the methodology ( such as , for example , US 10 , 265 , 349 B2 21 22 administration of a composition comprising a microbial about 60 % , or at least about 70 % , or at least about 80 % , or consortium as described herein ) . In one aspect , it is under at least about 90 % or up to and including a 100 % increase stood that prevention can also mean that the disease is not or any increase between 10 - 100 % as compared to a refer established to the extent that occurs in untreated controls . ence level, or at least about a 2 - fold , or at least about a For example , there can be a 5 , 10 , 15 , 20 , 25 , 30 , 35 , 40 , 50 , 5 3 - fold , or at least about a 4 - fold , or at least about a 5 - fold or 60 , 70 , 80 , 90 , or 100 % reduction in the establishment of at least about a 10 - fold increase , at least about a 20 - fold disease frequency relative to untreated controls . Accord increase , at least about a 50 - fold increase , at least about a ingly , prevention of a disease encompasses a reduction in the 100 - fold increase , at least about a 1000 - fold increase or likelihood that a subject will develop the disease, relative to more as compared to a reference level . an untreated subject ( e . g . a subject who is not treated with 10 The term “ pharmaceutically acceptable ” can refer to a composition comprising a microbial consortium as compounds and compositions which can be administered to described herein ) . a subject ( e . g ., a mammal or a human ) without undue As used herein , the term " full complement of bile acid toxicity . transformations ” refers to the metabolism of primary bile A s used herein , the term “ pharmaceutically acceptable acids to secondary bile acids . Bile acid transformations 15 carrier” can include any material or substance that , when performed by gut microbes include deconjugation , deglu - combined with an active ingredient, allows the ingredient to curonidation , oxidation of hydroxyl groups, reduction of retain biological activity and is non -reactive with the sub oxo groups to yield epimeric hydroxyl bile acids, esterifi- ject ' s immune system . Examples include, but are not limited cation and dehydroxylation . These reactions on bile acids to , any of the standard pharmaceutical carriers such as a are the full complement of bile acid transformations as the 20 phosphate buffered saline solution , emulsions such as oil / term is used herein . water emulsion , and various types of wetting agents . The " Synergy ” or “ synergistic interactions” refers to the inter - term " pharmaceutically acceptable carriers ” excludes tissue action or cooperation of two or more microbes to produce a culture media . combined effect greater than the sum of their separate As used herein , the term “ comprising ” means that other effects. For example , in one embodiment, " synergy ” 25 elements can also be present in addition to the defined between two or more microbes can result from a first elements presented . The use of " comprising ” indicates microbe secreting a waste product or metabolite that the inclusion rather than limitation . second microbe uses to fuel growth or other processes. As used herein the term " consisting essentially of” refers As used herein , the term “ persistence ” refers to the to those elements required for a given embodiment. The maintenance of one or more members of the microbial 30 term permits the presence of additional elements that do not consortium in the gastrointestinal tract at a number, biomass materially affect the basic and novel or functional charac or activity that is at or above the threshold for treating and / or teristic ( s ) of that embodiment of the invention . preventing food allergy . Persistence can be measured by The term “ consisting of” refers to compositions, methods , obtaining a stool sample to determine the number, biomass, and respective components thereof as described herein , and / or activity of one or more members of the microbial 35 which are exclusive of any element not recited in that consortium . In some embodiments , persistence can be mea - description of the embodiment . sured by obtaining a ratio of the measured biomass of at least Further, unless otherwise required by context, singular two members of the microbial consortium in the stool terms shall include pluralities and plural terms shall include sample . the singular. The terms “ decrease " , " reduced ” , “ reduction ", or 40 It should be understood that this invention is not limited " inhibit ” are all used herein to mean a decrease or lessening to the particular methodologies , protocols , and reagents , of a property , level , or other parameter by a statistically etc . , described herein and as such can vary therefrom . The significant amount . In some embodiments , “ reduce ," " reduc - terminology used herein is for the purpose of describing tion ” or “ decrease ” or “ inhibit” typically means a decrease particular embodiments only , and is not intended to limit the by at least 10 % as compared to a reference level ( e . g . , the 45 scope of the present invention , which is defined solely by the absence of a given treatment) and can include, for example , claims. a decrease by at least about 10 % , at least about 20 % , at least Microbial Flora about 25 % , at least about 30 % , at least about 35 % , at least Each individual has a personalized gutmicrobiota includ about 40 % , at least about 45 % , at least about 50 % , at least ing an estimated 500 to 5000 or more species of bacteria , about 55 % , at least about 60 % , at least about 65 % , at least 50 fungi, viruses , archaea and other microorganisms, up to 100 about 70 % , at least about 75 % , at least about 80 % , at least trillion individual organisms, that reside in the digestive about 85 % , at least about 90 % , at least about 95 % , at least tract, providing a host of useful symbiotic functions, for about 98 % , at least about 99 % , or more . As used herein , example , including aiding in digestion , providing nutrition “ reduction ” or “ inhibition ” does not encompass a complete for the colon , producing vitamins, regulating the immune inhibition or reduction as compared to a reference level. 55 system , assisting in defense against exogenous bacteria , “ Complete inhibition ” is a 100 % inhibition as compared to modulating energy metabolism , and the production of short a reference level . A decrease can be preferably down to a chain fatty acids (SCFAs ) , e . g ., via dietary carbohydrates , level accepted as within the range of normal for an indi- including resistant starches and dietary fiber, which are vidual without a given disorder. substrates for fermentation that produce SCFAs, primarily The terms “ increased ” , “ increase " or " enhance ” or “ acti - 60 acetate , propionate , succinate , butyrate , 1 , 2 propanediol or vate ” are all used herein to generally mean an increase of a 1 , 3 propanediol as end products . property , level , or other parameter by a statically significant An imbalance in the microbial flora found in and on the amount; for the avoidance of any doubt , the terms human body is known to be associated with a variety of " increased ” , “ increase " or " enhance " or " activate ” means an disease states. For example , obesity in both humans and increase of at least 10 % as compared to a reference level, for 65 experimental mouse models is associated with alterations in example an increase of at least about 20 % , or at least about the intestinal microbiota that appear to be pathogenic . In 30 % , or at least about 40 % , or at least about 50 % , or at least settings of ' dysbiosis ' or disrupted symbiosis , microbiota US 10 , 265 , 349 B2 23 24 functions that can be lost or deranged , resulting in increased In another embodiment, the strains of viable gut bacteria susceptibility to pathogens , include altered metabolic pro - are selected from the group consisting of: ( i ) Clostridium files , or induction of proinflammatory signals that can result ramosum , C . scindens, C . hiranonsis , C . bifermentans , C . in local or systemic inflammation or autoimmunity . In leptum , and C . sardiniensis , or ( ii ) Bacteroides fragilis , B . addition , in asthmatic subjects, both the bacterial burden and 5 thetaiotaomicron , B . ovatus, Parabacteroides goldsteinii , bacterial diversity were significantly higher as compared to and Prevotella tannerae. control subjects , which were also correlated with bronchial In one embodiment, the strains of viable gut bacteria do not include Escherichia coli , Klebsiella pneumoniae , Pro hyper - responsiveness . Thus, the intestinal microbiota plays teus mirabilis , Enterobacter cloacae , Bilophila wadswor a significant role in the pathogenesis ofmany diseases and 10 thia , Alistipes onderdonkii, Desulfovibrio species, Lactoba disorders , including a variety of pathogenic infections of the cillus johnsoni, and Parasutterella excrementihominis . gut. For instance , patients become more susceptible to In another embodiment, the consortium does not comprise pathogenic infections when the normal intestinal microbiota bacteria of the Genera Bilophila , Enterobacter, Escherichia , has been disturbed due to use of broad - spectrum antibiotics . Klebsiella , Proteus, Alistipes, Desulfovibrio , Blautia , or Many of these diseases and disordersrders are chronicchronic conditions 15 Parasutterella . that significantly decrease a patient' s quality of life and can In another embodiment, the consortium does not comprise be ultimately fatal. bacteria of the Families Desulfovibrionaceae , Enterobacte Microbial Consortia riaceae , Rikenellaceae , and Sutterellaceae . In some embodiments , a microbial consortium comprises In another embodiment, the consortium does not comprise at least 4 , at least 5 , at least 6 , at least 7 , at least 8 , at least 20 bacteria of the Families Lactobacillaceae or Enterbacteri 9 , at least 10 , at least 11 , at least 12 or more different viable , aceae . bacterial species, e . g ., 15 or more , 20 or more , 25 or more , In another embodiment, the consortium does not comprise 30 or more , or even 40 or more . In one embodiment, a bacteria of the Order Burkholdales , Desulfovibrionates , or microbial consortium comprises fewer than 40 species , e . g . , Enterobacteriales. 30 or fewer species , 25 or fewer species, 20 or fewer species, 25 Metabolic Features : Various features of gut microbes are or 15 or fewer species . In another embodiment, a minimal beneficial for protection from or therapy for allergy , includ microbial consortium comprises 12 or less , 11 or less, 10 or ing food allergy . In the following, features and correspond less , 9 or less , 8 or less, 7 or less, 6 or less , 5 or less , or 4 ing functions contemplated to render particular species or or less different viable bacterial species . In one embodiment, taxa of gut microbes well - suited for a protective or thera at least one ( e . g . , at least 2 , at least 3 , at least 4 , at least 5 , 30 peutic microbial consortium as described herein are at least 6 , at least 7 , at least 8 , 8 or fewer, 7 or fewer, 6 or described . In practice, a consortium comprising four or fewer, 5 or fewer , 4 or fewer , 3 or fewer, 2 or fewer ) of the more , e . g ., five or more , six or more , seven or more , eight bacterial constituents is a non - pathogenic bacterial strain . or more , nine or more or ten or more of these features and Also contemplated are consortia of 4 to 40 species , 4 to 30 corresponding functions is considered a likely candidate for species , 4 to 25 species , 4 to 20 species , 4 to 15 species, 4 35 protection or therapy for food allergy . to 11 species , 5 to 40 species , 5 to 30 species, 5 to 25 species, In some embodiments , the microbial consortium com 5 to 20 species, 5 to 15 species, 5 to 11 species , 6 to 40 prises one or more types ofmicrobes capable of producing species , 6 to 30 species, 6 to 25 species, 6 to 20 species, 6 butyrate in a mammalian subject. Butyrate - producing to 15 species, 6 to 11 species , 7 to 40 species, 7 to 30 species, microbes can be identified experimentally , e . g . , by NMR or 7 to 25 species , 7 to 20 species , 7 to 15 species , 7 to 11 40 gas chromatography analyses of microbial products or colo species , 8 to 40 species , 8 to 30 species , 8 to 25 species, 8 rimetric assays (Rose I A . 1955 . Methods Enzymol. 1 : to 20 species, 8 to 15 species, 8 to 11 species, 9 to 40 species, 591 - 5 ) . Butyrate - producing microbes can also be identified 9 to 30 species , 9 to 25 species , 9 to 20 species , 9 to 15 computationally , e . g ., by the identification of one or more species, 9 to 11 species, 10 to 40 species , 10 to 30 species, enzymes involved in butyrate synthesis . Non - limiting 10 to 25 species , 10 to 20 species , 10 to 15 species , or 10 to 45 examples of enzymes found in butyrate - producing microbes 11 species . include butyrate kinase , phosphotransbutyrylase , and In one embodiment, the at least 1 bacterial constituent of butyryl COA : acetate CoA transferase (Louis P . , et al. 2004 . a microbial consortium is a bacterial strain ( s ) of viable gut J Bact. 186 ( 7 ) : 2099 - 2106 ) . Butyrate -producing strains bacteria selected from the group consisting of: Clostridium include, but are not limited to , Clostridium sardiniensis , ramosum , Clostridium scindens, Clostridium hiranonsis , 50 Clostridium hiranonsis , Face?libacterium prausnitzii , Buty Clostridium bifermentans , Clostridium leptum , Clostridium rovibrio spp ., Eubacterium rectale , and Roseburia intesti sardiniensis, Bacteroides fragilis, Bacteroides thetaiotaomi- nalis . cron , Bacteroides ovatus, Parabacteroides goldsteinii , Pre - In some embodiments , a pharmaceutical composition votella tannerae, Clostridum hathewayi, Clostridum nexile , comprises two or more types of microbes or bacterial strains , Clostridium hylemonae , Clostridium glycyrrhizinilyticum , 55 wherein the at least two types of microbes are capable of Clostridium scindens, Clostridium lavalense , Clostridum producing butyrate in a mammalian subject. In other limetarium , Clostridium symbiosum , Clostridium spo embodiments , the composition comprises two or more types rosphaeroides, Dialister proprionicfaceins , Dialister succi- of microbes, wherein two or more types of microbe coop natiphilus, Parabacteroides distasonis , Parabacteroides erate ( i. e ., cross - feed ) to produce an immunomodulatory goldsteinii, Parabacteroides merdae, Peptostreptococcus 60 short chain fatty acid (SCFA ) ( e. g ., butyrate ) in a mamma anaerobius, Subdoligranulum variabile , and Veilonella ratti . lian subject. In one embodiment, the composition comprises In another embodiment, the strains of viable gut bacteria at least one type of microbe (e . g. , Bifidobacterium spp ., are selected from the group consisting of: Clostridium Bacteroides thetaiotaomicron , Bacteroides fragilis or ramosum , C . scindens , C . hiranonsis , C . bifermentans, C . Clostridium ramosum ) is capable of metabolizing a prebi leptum , C . sardiniensis , Bacteroides fragilis , B . thetaiotao - 65 otic , including but not limited to , inulin , inulin -type fructans , micron , B . ovatus , Parabacteroides goldsteinii , and Pre - fucose - containing glycoconjugates including the H1, H2 , votella tannerae . Lewis A , B , X , or Y antigens, or oligofructose , such that the US 10 ,265 , 349 B2 25 26 resulting metabolic product can be converted by a second subunits ); Kdd , 3 , 5 -diaminohexanoate dehydrogenase ; Kce , type ofmicrobe ( e . g ., a butyrate - producing microbe such as 3 -keto - 5 - aminohexanoate cleavage enzyme; Kal, 3 - amin Roseburia spp . ) to an immunomodulatory SCFA such as obutyryl- CoA ammonia lyase ; AbfH , 4 -hydroxybutyrate butyrate ( Falony G . , ET al. 2006 Appl. Environ . Microbiol . dehydrogenase ; AbfD , 4 - hydroxybutyryl - CoA dehydratase ; 72 ( 12 ) : 7835 - 7841 ) . In other aspects , the composition com - 5 Isom , vinylacetyl -CoA 3 , 2 -isomerase ( same protein as prises at least one acetate -consuming , butyrate -producing AbfD ) : 4Hbt, butyryl- CoA : 4 -hydroxybutyrate CoA trans microbe ( e . g . , Faecalibacterium prausnitzii or Roseburia ferase; But , butyryl- CoA : acetate CoA transferase; Ato , intestinalis ) . butyryl- CoA : acetoacetate CoA transferase ( a , ß subunits ) ; In some embodiments , the composition comprises one or Ptb , phosphate butyryltransferase ; Buk , and butyrate kinase more types of microbe capable of producing propionate 10 (see e . g . , Vital et al. mBIO 5 ( 2 ) : e00889 - 14 ) . and / or succinate in a mammalian subject, optionally further In some embodiments , a microbial consortium comprises comprising a prebiotic or substrate appropriate for propi- at least one bacterial species that produces compounds onate and / or succinate biosynthesis . Examples of prebiotics capable of stimulating the aryl hydrocarbon ( AhR ) receptor or substrates used for the production of propionate include, in gut epithelial cells , antigen -presenting cells and /or T cells. but are not limited to , L - rhamnose , D -tagalose , resistant 15 Without wishing to be bound by theory , stimulation of the starch , inulin , polydextrose , arabinoxylans, arabinoxylan AhR receptor can aid in the development of regulatory T cell oligosaccharides , mannooligosaccharides, and laminarans processes that can prevent and / or treat food allergy . Some (Hosseini E ., et al. 2011 . Nutrition Reviews. 69 ( 5 ) : 245 - 258 ) . non - limiting examples of compounds that stimulate host Propionate - producing microbes can be identified experi- aryl hydrocarbon receptor pathways include ( i ) indole , ( ii ) mentally , such as by NMR or gas chromatography analyses 20 intermediates from microbial synthesis of indole , trypto of microbial products or colorimetric assays (Rose I A . phan , tyrosine and histidine , ( iii ) microbial synthesis of 1955 . Methods Enzymol. 1 : 591 - 5 ) . Propionate -producing flavonoids, phenazines and / or quinones or (iv ) compounds microbes can also be identified computationally, such as by or intermediates of metabolism of host ingested flavonoids, the identification of one or more enzymes involved in phenazines and / or quinones . In one example , a viable , propionate synthesis . Non - limiting examples of enzymes 25 culturable , anaerobic gut bacterial strain produces aryl found in propionate - producing microbes include enzymes of hydrocarbon receptor agonists sufficient to stimulate host the succinate pathway, including but not limited to phos - aryl hydrocarbon receptor pathways comprises at least one phoenylpyruvate carboxykinase , pyruvate kinase, pyruvate gene associated with the synthesis of tryptophan or the carboxylase , malate dehydrogenase , fumarate hydratase , synthesis of quinone molecules . In an additional example, a succinate dehydrogenase , succinyl CoA synthetase , methyl - 30 viable , culturable , anaerobic gut bacterial strain that pro malonyl Coa decarboxylase , and propionate CoA trans - duces aryl hydrocarbon receptor agonists sufficient to stimu ferase , as well as enzymes of the acrylate pathway , including late host aryl hydrocarbon receptor pathways by microbial but not limited to L - lactate dehydrogenase , propionate COA synthesis of flavonoids, phenazines , and / or quinones . Thus transferase , lactoyl COA dehydratase, acyl CoA dehydroge - microbes that express or encode biosynthetic enzymes that nase , phosphate acetyltransferase , and propionate kinase . 35 participate in the synthesis of flavonoids , phenazines and / or For example , microbes that utilize the succinate pathway quinones are identified as microbes that produce host aryl include certain species of the Bacteroides genus , such as hydrocarbon receptor agonists . In one embodiment, the Bacteroides fragilis , Clostridium sardiniensis and Clostri- biosynthetic enzymes include the last enzyme in the path dum hiranonsis . In one embodiment, the propionate- produc - way that catalyzes the final biosynthetic reaction producing ing species is Bacteroides fragilis , Bacteroides thetaiotao - 40 e . g . , flavonoids, phenazine or quinone compounds . micron , or Bacteroides ovatus . In one embodiment, the In some embodiments , a microbial consortium comprises succinate - producing species is Bacteroides fragilis , Bacte - at least one bacterial species that produces compounds roides thetaiotaomicron , or Bacteroides ovatus. capable of stimulating the pregnane X receptor that e . g . , has Functional methods to define species that produce beneficial effects on gut barrier function and /or the devel butyrate , propionate and / or succinate includes analysis of 45 Opment of regulatory T cell processes . Non - limiting short - chain fatty acid ( SCFA ) production using gas - chroma - examples of compounds that stimulate the pregnane X tography / liquid chromatography (GC /LC ) to identify propi- receptor include (i ) desmolase , ( ii ) compounds or interme onate , butyrate , and / or succinate or mass spectroscopy based diates of hydroxysteroid dehydrogenase activity , or ( iii ) methods to detect these SCFA , as well as 1 , 2 -propanediol , compounds or intermediates derived from flavonoid and 1 , 3 -propanediol . Studies can be performed in cultured 50 metabolism enzymes. Thus , bacteria that encode and express supernatants from colonized gnotobiotic mice and from steroid desmolase and /or hydroxysteroid dehydrogenase conventional patients and / or animal samples . enzymes are expected to produce compounds that stimulate Additional methods for identifying species that produce the pregnane X receptor. Clostridium sardiniensis and butyrate comprise those species expressing butyryl - CoA : Clostridium scindens are non - limiting examples of bacterial acetate CoA transferases (But genes ) or butyrate kinases 55 species that produce compounds capable of stimulating the (Buk genes ) for production of butyrate from anaerobic pregnane X receptor. fermentation of sugars . In another embodiment , organisms In some embodiments , the microbial consortium com producing butyrate ( from amino acids such as lysine , glut- prises at least one bacterial species that produces compounds arate or 4 -aminobutyrate pathways ) express enzymes capable of stimulating the RAR - related orphan receptor including e . g . , L2Hgdh , 2 -hydroxyglutarate dehydrogenase ; 60 gamma (RORgamma ) pathways , for example , to stimulate Gct , glutaconate CoA transferase ( a , B subunits ) ; HgCoAd , development of regulatory T cell responses via direct stimu 2 -hydroxy - glutaryl- CoA dehydrogenase ( A , B , y subunits ) ; lation of RORgamma- activated pathways in gut antigen God , glutaconyl- CoA decarboxylase ( a , ß subunits) ; Th1 , presenting cells and /or epithelial cells that then stimulate thiolase ; hbd , B -hydroxybutyryl - CoA dehydrogenase ; Cro , regulatory T cell responses . In one embodiment, the viable , crotonase; Bcd , butyryl- CoA dehydrogenase ( including 65 culturable , anaerobic gut bacterial strain that produces com electron transfer protein a , B subunits ) ; KamA , lysine - 2 , 3 - pounds endogenously or by metabolizing ingested precur aminomutase ; KamD , E , B - lysine -5 ,6 - aminomutase ( a , ß sors , that is capable of stimulating the RORgamma (RAR US 10 , 265, 349 B2 27 28 related orphan receptor gamma) pathways to stimulate mediated by Toll- like receptors ( TLR ), CD14 and /or lipid development of regulatory T cell responses is a strain that binding proteins in antigen presenting cells , gut epithelial expresses at least one cholesterol reductase and other cells and / or T cells to promote the development of regula enzymes capable of metabolizing sterol compounds. Non tory T cells . Non - limiting examples of TLR agonists include limiting examples ofmicrobes that produce compounds that 5 lipopolysaccharide (LPS ) , exopolysaccharides (PSA ) , pep stimulate the RORgamma pathway include Clostridium tidoglycan or CpG motifs produced by commensal members scindens , Clostridia hiranonsis , and Clostridium sardinien sis . In one instance , those species express bile acid trans of Bacteroides, or lipoteichoic acids (LTA ) produced by forming enzymes that can also produce RORgamma path members of Clostridium . In one embodiment, an anaerobic way agonists. 10 gut bacterial strain that acts as a TLR agonist is selected In some embodiments , a microbial consortium described from the following Table . herein improves gut function , for example, by stimulating host mucins and complex glycoconjugates and improving Family Genus Species colonization by protective commensal strains. In one embodiment, the microbial consortium comprises at least 15 Clostridieaceae Clostridium , Hungatella Hungatella hathawayi Eubacteriaceae Eubacterium Eubacterium rectale one bacterial strain , such as Bacteroides thetaiotaomicron , Erysipelotrichaceae Erysipelatoclostridium Erysipelatoclostridium that stimulates production of mucins and complex glyco ( formerly species in ramosum ( Clostridium conjugates by the host . genus Clostridium ) ramosum ) Immunomodulation : Other exemplary compositions use - Lachnospiraceae Blautia , Butyrovibrio , Butyrovibrio crossatus, Cellulosyliticum , Roseburia intestinalis , ful for treatment of food allergy contain bacterial strains 20 Clostridium cluster Clostridium scindens, capable of altering the proportion of immune subpopula XIVa species , Clostridium hylemonde , tions, e .g ., T cell subpopulations, e. g. , Tregs in the subject. Coprococcus, Dorea , Clostridium symbiosum For example , immunomodulatory bacteria can increase or Lachnospira, Robinsonella , decrease the proportion of Treg cells, Th17 cells , Th1 cells , Roseburia , or Th2 cells in a subject. The increase or decrease in the 25 Ruminococcaceae Faecalobacterium , Faecalibacterium proportion of immune cell subpopulations can be systemic , Ruminococcus, prausnitzii, Subdoligranulum , Subdoligranulum or it can be localized to a site of action of the colonized Clostridium cluster variabile consortium , e . g . , in the gastrointestinal tract or at the site of XIVa species a distal dysbiosis . In some embodiments, a microbial con Bacteroidaceae Bacteroides Bacteroides sortium comprising immunomodulatory bacteria is used for 30 thetaiotaomicron , treatment of food allergy based on the desired effect of the Bacteroides fragilis , Bacteroides ovatus probiotic composition on the differentiation and / or expan Prophyromona Parabacteroides, Parabacteroides sion of subpopulations of immune cells in the subject. daceae Porphyromonas, goldsteinii, In one embodiment, the microbial consortium contains Tannerella Parabacteroides immunomodulatory bacteria that increase the proportion of 35 merdae , Parabacteroides Treg cells in a subject or in a particular location in a subject, distasonis e . g ., the gut tissues . In one embodiment, a microbial con Prevotellaceae Prevotella Prevotella tannerae sortium contains immunomodulatory bacteria that increase the proportion of Th17 cells in a subject. In another embodi ment, a microbial consortium contains immunomodulatory 40 . Bile Acid Transformation : Primary bile acids ( e . g . , cholic bacteria that decrease the proportion of Th17 cells in and chenodeoxycholic acids in humans ) are generated in the subject . In one embodiment, a microbial consortium con - liver of mammals , including humans ,mainly by conjugation tains immunomodulatory bacteria that increase the propor - with the amino acids taurine or glycine , and are secreted in tion of Th1 cells in a subject. In another embodiment, a bile . In the intestinal tract, primary bile acids are metabo microbial consortium contains immunomodulatory bacteria 45 lized by microbes that transform the primary bile acids to that decrease the proportion of Th1 cells in a subject. In one secondary bile acids. Intestinal microbial transformation of embodiment, a microbial consortium contains immuno - primary bile acids can include deconjugation , deglucuroni modulatory bacteria that increase the proportion of Th2 cells d ation , oxidation of hydroxyl groups, reduction of oxo in a subject. In another embodiment, a microbial consortium groups to yield epimeric hydroxyl bile acids , esterification , contains immunomodulatory bacteria that decrease the pro - 50 and dehydroxylation . Non -limiting examples of bacteria that portion of Th2 cells in a subject . perform deconjugation of primary bile acids include Bacte In one embodiment, a microbial consortium contains immunomodulatory bacteria capable of modulating the pro roides, Bifidobacterium , Clostridium , and Lactobacillus . portion of one or more of Treg cells , Th17 cells , Th1 cells , Non - limiting examples of bacteria that perform oxidation Th2 cells , and combinations thereof in a subject . Certain 55 and epimerization of primary bile acids include Bacteroides, immune cell profiles can be particularly desirable to treat or Clostridium , Egghertella , Eubacterium , Peptostreptococ prevent inflammatory disorders, such as food allergies . For cus , and Ruminococcus . Non - limiting examples of bacteria example , in some embodiments , treatment or prevention of that perform 7 - dehydroxylation of primary bile acids include e . g . , food allergy can be promoted by increasing numbers of Clostridium , and Eubacterium . Non - limiting examples of Treg cells and Th2 cells , and decreasing numbers of Th17117 60 bacteriabac that perform esterification of primary bile acids cells and Th1 cells . Accordingly , a microbial consortium for include Bacteroides , Eubacterium , and Lactobacillus . the treatment or prevention of food allergy can contain a In one embodiment, a microbial consortium as described microbial consortium capable of promoting Treg cells and herein comprises at least one bacterial constituent that Th2 cells , and reducing Th17 and Th1 cells . transforms bile acids by deconjugation . In another embodi In one embodiment, the anaerobic gut bacterial strain in 65 ment, a microbial consortium as described herein comprises the methods and compositions described herein express at least one bacterial constituent that transforms bile acids by agonists capable of binding to and modulating responses 7 -dehydroxylation . In another embodiment, a microbial con US 10 , 265 , 349 B2 29 30 sortium as described herein comprises at least one bacterial Clostridium cadaveric , Clostridium chauvoei, Clostridium constituent that transforms bile acids by esterification . clostridioforme, Clostridium cochlearium , Clostridium dif In one embodiment, a microbial consortium as described ficile , Clostridium haemolyticum , Clostridium hastiforme, herein comprises at least 2 , at least 3 , at least 4 , at least 5 , Clostridium histolyticum , Clostridium indolis , Clostridium at least 6 , at least 7 , at least 8 , at least 9 , at least 10 , at least 5 irregulare , Clostridium limosum , Clostridium malenomina 11 or more bacterial constituents that perform bile acid tum , Clostridium novyi , Clostridium oroticum , Clostridium transformation . paraputrificum , Clostridium perfringens, Clostridium pili In one embodiment, a microbial consortium as described forme, Clostridium putrefaciens , Clostridium putrificum , herein comprises 11 or fewer, 10 or fewer , 9 or fewer, 8 or Clostridium septicum , Clostridium sordellii , Clostridium fewer, 7 or fewer, 6 or fewer , 5 or fewer , 4 or fewer, 3 or 10 sphenoides, and Clostridium tetani. fewer , 2 or fewer 1 or fewer or zero bacterial constituents In another embodiment, the bacterial composition does that perform bile acid transformation , such as deconjugation , not comprise at least one of Escherichia coli , and Lactoba esterification or 7 -dehydroxylation . cillus johnsonii. In one embodiment, a microbial consortium comprises at In another embodiment, the bacterial composition does least one anaerobic gut bacterial strain that alone, or in 15 not comprise at least one of Clostridium innocuum , combination , performs the full complement of bile acid Clostridium butyricum , Escherichia coli , and Blautia pro transformations . ducta (previously known as Peptostreptococcus productus ). Engineered microbes : In some embodiments , one or more In another embodiment, the bacterial composition does members of the microbial consortium comprises an engi- not comprise at least one of Eubacteria , Fusobacteria , neered microbe ( s) . For example , engineered microbes 20 Propionibacteria , Escherichia coli, and Gemmiger. include microbes harboring i ) one or more introduced In another embodiment, the compositions described genetic changes , such change being an insertion , deletion , herein do not comprise pathogenic bacteria such as e . g . , translocation , or substitution , or any combination thereof, of Yersinia , Vibrio , Treponema, Streptococcus, Staphylococ one or more nucleotides contained on the bacterial chromo - cus , Shigella , Salmonella , Rickettsia , Orientia , Pseudomo some or on an endogenous plasmid , wherein the genetic 25 nas, Neisseria , Mycoplasma , Mycobacterium , Listeria , Lep change can result in the alteration , disruption , removal, or tospira , Legionella , Klebsiella , Helicobacter, Haemophilus , addition of one or more protein coding genes, non -protein - Francisella , Escherichia , Ehrlichia , Enterococcus , Cox coding genes , gene regulatory regions, or any combination ella , Corynebacterium , Chlamydia , Chlamydophila . thereof, and wherein such change can be a fusion of two or Campylobacter , Burkholderia , Brucella , Borrelia , Borde more separate genomic regions or can be synthetically 30 tella , Bacillus, multi- drug resistant bacteria , extended spec derived ; ii ) one or more foreign plasmids containing a trum beta - lactam resistant Enterococci ( ESBL ) , Car mutant copy of an endogenous gene , such mutation being an bapenem -resistant Enterobacteriaceae (CRE ) , and insertion , deletion , or substitution , or any combination vancomycin -resistant Enterococci (VRE ) . thereof, of one or more nucleotides; and iii ) one or more In other embodiments , the compositions described herein foreign plasmids containing a mutant or non -mutant exog - 35 do not comprise pathogenic species or strains , such as enous gene or a fusion of two or more endogenous, exog - Aeromonas hydrophila , Campylobacter fetus, Plesiomonas enous, or mixed genes. The engineered microbe( s) can be shigelloides, Bacillus cereus, Campylobacter jejuni, produced using techniques including but not limited to Clostridium botulinum , Clostridium difficile , Clostridium site - directed mutagenesis , transposon mutagenesis , knock - perfringens, enteroaggregative Escherichia coli , enterohe outs , knock - ins, polymerase chain reaction mutagenesis , 40 morrhagic Escherichia coli , enteroinvasive Escherichia coli, chemical mutagenesis , ultraviolet light mutagenesis , trans - enterotoxigenic Escherichia coli ( such as, but not limited to , formation (chemically or by electroporation ) , phage trans - LT and/ or ST ) , Escherichia coli 0157 :H7 , Helicobacter duction , or any combination thereof . pylori, Klebsiellia pneumonia , Lysteria monocytogenes , Ple Excluded Bacteria : In one embodiment, a microbial con siomonas shigelloides, Salmonella spp . , Salmonella typhi, sortium does not include an organism conventionally clas - 45 Salmonella paratyphi, Shigella spp . , Staphylococcus spp . , sified as a pathogenic or opportunistic organism . It is pos - Staphylococcus aureus, vancomycin - resistant enterococcus sible that a function shared by all members of a given spp . , Vibrio spp. , Vibrio cholerae , Vibrio parahaemolyticus , taxonomic group could be beneficial, e . g . , for providing Vibrio vulnificus , and Yersinia enterocolitica . particular metabolites, yet for other reasons the overall effect In one embodiment, the microbial consortia and compo of one or more particular members of the group is not 50 sitions thereof do not comprise Escherichia coli, Klebsiella beneficial and is , for example , pathogenic . Clearly , members pneumoniae , Proteus mirabilis, Enterobacter cloacae, and / of a given taxonomic group that cause pathogenesis , e . g ., or Bilophila wadsworthia . acute gastrointestinal pathologies, are to be excluded from Reduction of pathogenic organisms: In some embodi the therapeutic or preventive methods and compositions ments , compositions comprising a microbial consortium as described herein . described herein offer a protective or therapeutic effect In one embodiment, the bacterial composition does not against dysbiosis or against infection by one or more GI comprise at least one of: Acidaminococcus intestinalis , pathogens of interest. In one embodiment , a microbial Escherichia coli, Lactobacillus casei, Lactobacillus para consortium as described herein reduces the biomass of one casei, Raoultella sp . , and Streptococcus mitis . or more dysbiotic or pathogenic bacterial strains . In another embodiment, the bacterial composition does 60 In one embodiment, a microbial consortium as described not comprise at least one of Bamesiella intestinihominis ; herein decreases the biomass of one or more dysbiotic or Lactobacillus reuteri ; Enterococcus hirae , Enterococus pathogenic bacterial strains by at least 10 % compared to the faecium , or Enterococcus durans, Anaerostipes caccae or biomass of the one or more dysbiotic or pathogenic bacterial Clostridium indolis ; Staphylococcus wameri or Staphylo - strains in the absence of treatment with such microbial coccus pasteuri; and Adlercreutzia equolifaciens. 65 consortium . In other embodiments the biomass of one or In another embodiment, the bacterial composition does more pathogenic bacterial strains is decreased by at least not comprise at least one of Clostridium botulinum , 20 % , at least 30 % , at least 40 % , at least 50 % , at least 60 % , US 10 , 265 , 349 B2 31 32 at least 70 % , at least 80 % , at least 90 % , at least 95 % , at least inhibit the growth of a given pathogenic or dysbiotic 99 % , or even 100 % ( i. e ., below detectable limits of the microbe. The assay can operate in automated high - through assay ) as compared to the biomass of the dysbiotic or put or manual modes . Under either system , human or animal pathogenic bacterial strains in the gut of the subject prior to feces can be re -suspended in an anaerobic buffer solution , treatment with the microbial consortium or compositions 5 such as pre -reduced PBS or other suitable buffer, the par thereof. ticulate removed by centrifugation , and filter sterilized . This In some embodiments , a microbial consortium as 10 % sterile- filtered feces material serves as the base media described herein alters the gut environment such that the for the in vitro assay. To test a bacterial composition , an number, biomass, or activity of one or more dysbiotic or investigator can add it to the sterile - filtered feces material pathogenic organisms is decreased by at least 10 % ( e . g ., at 10 for a first incubation period and then can inoculate the least 20 % , at least 30 % , at least 40 % , at least 50 % , at least incubated microbial solution with a pathogenic or dysbiotic 60 % , at least 70 % , at least 80 % , at least 90 % , at least 95 % , microbe of interest for a second incubation period . The at least 99 % , or even 100 % (i . e. , below detectable limits of resulting titer of the pathogenic or dysbiotic microbe is the assay ) ) . As but one example , colonization of Bacteroides quantified by any number of methods such as those reduces the biomass of dysbiotic species in the Enterobac - 15 described below , and the change in the amount of pathogen teriaceae or Desulfonovibriacaea Families . is compared to standard controls including the pathogenic or In some embodiments , the pathogenic bacterium is dysbiotic microbe cultivated in the absence of the bacterial selected from the group consisting of Yersinia , Vibrio , composition . The assay is conducted using at least one Treponema , Streptococcus, Staphylococcus, Escherichial control. Feces from a healthy subject can be used as a Shigella , Salmonella , Rickettsia , Orientia , Pseudomonas, 20 positive control. As a negative control, antibiotic - treated Neisseria , Mycoplasma , Mycobacterium , Listeria , Lep - feces or heat -treated feces can be used . Various bacterial tospira , Legionella , Klebsiella , Helicobacter, Haemophilus, compositions can be tested in this material and the bacterial Francisella , Escherichia , Ehrlichia , Enterococcus, Cox compositions optionally compared to the positive and /or iella , Corynebacterium , Clostridium , Chlamydia , Chlamy - negative controls . The ability to inhibit the growth of a dophila , Campylobacter , Burkholderia , Brucella , Borrelia , 25 pathogenic or dysbiotic microbe can be measured by plating Bordetella , Bifidobacterium , Bacillus, Bilophila , Desulfovi- the incubated material on selective media and counting brio , multi -drug resistant bacteria , extended spectrum beta - colonies . After competition between the bacterial composi lactam resistant Enterococci ( ESBL ) , Carbapenem - resistant tion and the pathogenic or dysbiotic microbe , each well of Enterobacteriaceae (CRE ) , and vancomycin - resistant the in vitro assay plate is serially diluted ten - fold six times , Enterococci (VRE ) . 30 and plated on selective media . For Clostridium difficile this In some embodiments, these pathogens include , but are would include , for example , cycloserine cefoxitin mannitol not limited to , Aeromonas hydrophila , Campylobacter fetus, agar ( CCMA ) or cycloserine cefoxitin fructose agar Plesiomonas shigelloides, Bacillus cereus, Campylobacter ( CCFA ) , and incubated . Colonies of the pathogenic or jejuni, Clostridium botulinum , Clostridium difficile , dysbiotic microbes are then counted to calculate the con Clostridium perfringens , enteroaggregative Escherichia 35 centration of viable cells in each well at the end of the coli , entero hemorrhagic Escherichia coli , enteroinvasive competition . Escherichia coli, enterotoxigenic Escherichia coli ( such as, Alternatively , the ability to inhibit the growth of a patho but not limited to , LT and / or ST ) , Escherichia coli 0157: H7 , genic or dysbiotic species can be measured by quantitative Helicobacter pylori , Klebsiellia pneumonia , Lysteria mono - PCR (qPCR ). Standard techniques can be followed to gen cytogenes, Plesiomonas shigelloides, Salmonella spp . , Sal - 40 erate a standard curve for the pathogenic or dysbiotic strain monella typhi, Salmonella paratyphi, Shigella spp ., Staphy - of interest. Genomic DNA can be extracted from samples lococcus spp . , Staphylococcus aureus, vancomycin - resistant using commercially - available kits , such as the Mo Bio enterococcus spp . , Vibrio spp . , Vibrio cholerae , Vibrio para - Powersoil® -htp 96 Well Soil DNA Isolation Kit (Mo Bio haemolyticus, Vibrio vulnificus , and Yersinia enterocolitica . Laboratories , Carlsbad , Calif. ) , the Mo Bio Powersoil® In one embodiment, the pathogen of interest is at least one 45 DNA Isolation Kit (Mo Bio Laboratories , Carlsbad , Calif .) , pathogen chosen from Clostridium difficile , Salmonella spp ., or the QIAamp DNA Stool Mini Kit ( QIAGEN , Valencia , pathogenic Escherichia coli, vancomycin -resistant Entero - Calif .) according to the manufacturer ' s instructions . The coccus spp ., and extended spectrum beta -lactam resistant qPCR can be conducted using HotMasterMix (5PRIME , Enterococci ( ESBL ). Gaithersburg , Md. ) and primers specific for the pathogenic Methods for testing the efficacy of the compositions 50 or dysbiotic microbe of interest, and can be conducted on a comprising a microbial composition to reduce the number, MicroAmp® Fast Optical 96 -well Reaction Plate with Bar biomass , or activity of one or more dysbiotic or pathogenic code ( 0 . 1 mL ) (Life Technologies , Grand Island , N . Y . ) and organisms are discussed in the following . While certain of performed on a BioRad C1000TM Thermal Cycler equipped the methods are described in the following in terms of with a CFX96TM Real- Time System ( BioRad , Hercules , assaying reduced number , biomass or activity of C . difficile , 55 Calif .) , with fluorescent readings of the FAM and ROX one of skill in the art can readily adapt the methods to channels . The Cq value for each well on the FAM channel measure the number, biomass or activity of one or more is determined by the CFX ManagerTM software version 2 . 1 . further microbial strains . The log10 (cfu /ml ) of each experimental sample is calculated In one embodiment , provided is an In Vitro Assay utiliz - by inputting a given sample ' s Cq value into linear regression ing competition between the bacterial compositions or sub - 60 model generated from the standard curve comparing the Cq sets thereof and C . difficile or other dysbiotic or pathogenic values of the standard curve wells to the known logio strain . This test in known in the art and as such is not (cfu / ml) of those samples . The skilled artisan can employ described in detail herein . alternative qPCR modes . In another embodiment, provided is an In Vitro Assay Also provided are In Vivo Assays establishing the pro utilizing 10 % (wt / vol ) Sterile - Filtered Feces. This assay 65 tective effect of bacterial compositions. The assay is tests for the protective effect of the bacterial compositions described in terms of protective effect against Clostridium and screens in vitro for combinations of microbes that difficile , but can be adapted by one of skill in the art for other US 10 ,265 , 349 B2 33 34 pathogens or dysbiotic species . Provided is an in vivo mouse at least 30 % , at least 40 % , at least 50 % , at least 60 % , at least model to test for the protective effect of the bacterial 70 % , at least 80 % , at least 90 % , at least 1 - fold , at least compositions against C . difficile . In this model (based on 2 - fold , at least 5 - fold , at least 10 - fold , at least 50 - fold , at Chen , et al. , Gastroenterology 135 (6 ) : 1984 - 1992 ( 2008 ) ) , least 100 - fold , at least 500 - fold , at least 1000 - fold , at least mice are made susceptible to C . difficile by a 7 day treatment 5 5000 - fold , at least 10 ,000 - fold , at least 15 ,000 - fold or at ( days - 12 to - 5 of experiment ) with 5 to 7 antibiotics least 20 , 000 - fold ) . For example , the microbial consortium ( including kanamycin , colistin , gentamycin , metronidazole stimulates the host ' s production of mucins and complex and vancomycin and optionally including ampicillin and glycoconjugates to improve gut barrier function and colo ciprofloxacin ) delivered via their drinking water, followed nization of beneficial organisms, additional probiotic com by a single dose with Clindamycin on day - 3 , then chal- 10 positions, or the microbial consortium itself . In some lenged three days later on day O with 104 spores of C . difficile embodiments , the microbial composition for enhancing the via oral gavage ( i. e ., oro - gastric lavage ) . Bacterial compo - biomass and/ or activity of beneficial organisms comprises sitions can be given either before ( prophylactic treatment ) or e . g . , Bacteroides thetaiotaomicron , which enhances coloni after (therapeutic treatment) C . difficile gavage . Further, zation by other Bacteroidetes and Clostridiales. In some bacterial compositions can be given after ( optional) vanco - 15 embodiments , the microbial consortium influences gut pH , mycin treatment to assess their ability to prevent recurrence reduction of oxygen tension , secretion of glycosidases, and and thus suppress the pathogen in vivo . The outcomes improving the reduction potential of the gut lumen to assessed each day from day - 1 to day 6 (or beyond , for improve the colonization of beneficial organisms. prevention of recurrence ) are weight, clinical signs , mortal- In another embodiment, the beneficial species comprises ity and shedding of C . difficile in the feces . Weight loss , 20 a Clostridium spp , such as Clostridium ramosum , clinical signs of disease and C . difficile shedding are typi- Clostridium scindens, Clostridium hiranonsis , Clostridium cally observed without treatment. Vancomycin provided by bifermentans, Clostridium leptum , Clostridium sardiniensis, oral gavage on days – 1 to 4 protects against these outcomes Clostridium hathewayi, Clostridium nexile , Clostridium and serves as a positive control. Clinical signs are subjec - hylemonae , Clostridium glycyrrhizinilyticum , Clostridium tive , and scored each day by the same experienced observer. 25 lavalense , Clostridium fimetarium , Clostridium symbiosum , Animals that lose greater than or equal to 25 % of their body or Clostridium sporosphaeroides. weight are euthanized and counted as infection - related mor - Characterization of Bacteria and Bacterial Consortia talities . Feces are gathered from mouse cages (5 mice per I n certain embodiments , methods are provided for testing cage ) each day , and the shedding of C . difficile spores is certain characteristics of compositions comprising a micro detected in the feces using a selective plating assay as 30 bial consortium . For example, the sensitivity of bacterial described for the in vitro assay above , or via qPCR for the compositions to certain environmental variables is deter toxin gene. The effects of test materials including 10 % mined , e . g ., in order to select for particular desirable char suspension of human feces (as a positive control) , bacterial acteristics in a given composition , formulation and /or use . compositions, or PBS (as a negative vehicle control) , are For example , the bacterial constituents of the composition determined by introducing the test article in a 0 . 2 mL 35 can be tested for pH resistance , bile acid resistance , and/ or volume into the mice via oral gavage on day - 1 , one day antibiotic sensitivity , either individually on a constituent prior to C . difficile challenge, on day 1, 2 and 3 as treatment by - constituent basis or collectively as a bacterial composi or post- vancomycin treatment on days 5 , 6 , 7 and 8 . Van - tion comprised of multiple bacterial constituents ( collec comycin , as discussed above , is given on days 1 to 4 as tively referred to in this section as a microbial consortium ) . another positive control. Alternative dosing schedules and 40 pH Sensitivity Testing : If a pharmaceutical composition routes of administration ( e . g . rectal) may be employed , will be administered other than to the colon or rectum ( i . e . , including multiple doses of test article , and 10 % to 1013 of a for example , an oral route ) , optionally testing for pH resis given organism or composition may be delivered . tance enhances the selection of microbes or therapeutic Enhancement of beneficial organisms: In some embodi compositions that will survive at the highest yield possible ments , compositions comprising a microbial consortium 45 through the varying pH environments of the distinct regions offer a therapeutic effect of enhancing beneficial organisms of the GI tract or genitourinary tracts. Understanding how in the GI tract . In one embodiment, a microbial consortium the bacterial compositions react to the pH of the GI or as described herein increases the biomass of one or more genitourinary tracts also assists in formulation , so that the beneficial bacterial strains by at least 10 % . In other embodi- number of microbes in a dosage form can be increased if ments the biomass of one or more beneficial bacterial strains 50 beneficial and / or so that the composition can be adminis is increased by at least 20 % , at least 30 % , at least 40 % , at t ered in an enteric - coated capsule or tablet or with a buff least 50 % , at least 60 % , at least 70 % , at least 80 % , at least e ring or protective composition . 90 % , at least 1- fold , at least 2 - fold , at least 5 - fold , at least As the pH of the stomach can drop to a pH of 1 to 2 after 10 - fold , at least 50 - fold , at least 100 - fold , at least 500 - fold , a high -protein meal for a short time before physiological at least 1000 -fold , at least 5000 -fold , at least 10 ,000 -fold , at 55 mechanisms adjust it to a pH of 3 to 4 and often resides at least 15 ,000 - fold or at least 20 , 000 - fold over the biomass of a resting pH of 4 to 5 , and as the pH of the small intestine the beneficial bacterial strains in the gut of the subject prior can range from a pH of 6 to 7 . 4 , bacterial compositions can to treatment with the microbial consortium or compositions be prepared that survive these varying pH ranges ( specifi thereof. In one embodiment, the beneficial organisms are cally wherein at least 1 % , 5 % , 10 % , 15 % , 20 % , 25 % , 30 % , commensal bacterial strains that currently reside or exist in 60 40 % , 50 % , 60 % , 70 % , 80 % , 90 % , or as much as 100 % of the gut . In another embodiment , the beneficial organisms are the bacteria can survive gut transit times through various pH one or more of the bacterial strains in the microbial consor - ranges ) . This can be tested by exposing the bacterial com tium itself . position to varying pH ranges for the expected gut transit In some embodiments , a microbial consortium as times through those pH ranges . Therefore , as a non - limiting described herein alters the gut environment such that the 65 example only, 18 -hour cultures of compositions comprising number , biomass , or activity of one or more beneficial one or more bacterial species or strains can be grown in organisms is increased by at least 10 % ( e. g ., by at least 20 % , standard media , such as gut microbiota medium (“ GMM ” , US 10 , 265 , 349 B2 35 36 see Goodman et al ., PNAS 108 ( 15 ) :6252 - 6257 ( 2011 )) or In other embodiments , immunomodulatory bacteria are another animal- products - free medium , with the addition of identified by screening bacteria to determine whether the pH adjusting agents for a pH of 1 to 2 for 30 minutes , a pH bacteria induce secretion of pro - inflammatory or anti- in of 3 to 4 for 1 hour , a pH of 4 to 5 for 1 to 2 hours, and a flammatory cytokines by host cells . For example , human or pH of 6 to 7 . 4 for 2 . 5 to 3 hours . An alternative method for 5 mammalian cells capable of cytokine secretion , such as testing stability to acid is described in e . g ., U . S . Pat. No. immune cells ( e . g ., PBMCs, macrophages, T cells , etc . ) can be exposed to candidate immunomodulatory bacteria , or 4 ,839 , 281. Survival of bacteria can be determined by cul supernatants obtained from cultures of candidate immuno turing the bacteria and counting colonies on appropriate modulatory bacteria , and changes in cytokine expression or selective or non -selective media . ne 10 secretion can be measured using standard techniques, such Bile Acid Sensitivity Testing : Additionally , in some as ELISA , immunoblot , LuminexTM , antibody array, quan embodiments , testing for bile -acid resistance enhances the titative PCR , microarray , etc . Bacteria can be selected for selection of microbes or therapeutic compositions that will inclusion in a microbial consortium based on the ability to survive exposures to bile acid during transit through the GI induce a desired cytokine profile in human or mammalian tract . Bile acids are secreted into the small intestine and can1 , 15 cells . For example , anti- inflammatory bacteria can be like pH , affect the survival of bacterial compositions. This selected for inclusion (or alternatively exclusion ) in a micro can be tested by exposing the compositions to bile acids for bial consortium or composition thereof, based on the ability the expected gut exposure time to bile acids. For example , to induce secretion of one or more anti - inflammatory cytok bile acid solutions can be prepared at desired concentrations ines , and /or the ability to reduce secretion of one or more using 0 .05 mM Tris at pH 9 as the solvent. After the bile acid 20 pro - inflammatory cytokines . Anti- inflammatory cytokines is dissolved , the pH of the solution can be adjusted to 7 . 2 include , for example , IL - 10 , IL - 13 , IL - 9 , IL - 4 , IL - 5 , and with 10 % HCl. Bacterial components of the therapeutic combinations thereof. Other inflammatory cytokines compositions can be cultured in 2 . 2 ml of a bile acid include, for example , TGFB . Pro - inflammatory cytokines composition mimicking the concentration and type of bile include , for example , IFNY, IL - 12p70 , IL - la , IL - 6 , IL - 8 , acids in the patient, 1 . 0 ml of 10 % sterile - filtered feces 25 MCP1 , MIPla , MIP1B , TNFa , and combinations thereof. In media and 0 . 1 ml of an 18 -hour culture of the given strain some embodiments , anti - inflammatory inflammatory bacte of bacteria . Incubations can be conducted for from 2 .5 to 3 ria can be selected for inclusion in a microbial consortium hours or longer. An alternative method for testing stability to based on the ability to modulate secretion of one or more bile acid is described in e . g . , U .S . Pat. No . 4 ,839 , 281 . anti -inflammatory cytokines and / or the ability to reduce Survival of bacteria can be determined by culturing the 30 secretion of one or more pro -inflammatory cytokines by a bacteria and counting colonies on appropriate selective or host cell induced by a bacteria of a different type ( e . g . , a non - selective media . bacteria from a different species or from a different strain of Antibiotic Sensitivity Testing : As a further optional sen - the same species ) . sitivity test , the bacterial components of the microbial com In other embodiments , immunomodulatory bacteria are positions can be tested for sensitivity to antibiotics . In one 35 identified by screening bacteria to determine whether the embodiment, the bacterial components can be chosen so that bacteria impact the differentiation and /or expansion of par they are sensitive to antibiotics such that if necessary they ticular subpopulations of immune cells . For example , can can be eliminated or substantially reduced from the patient' s didate bacteria can be screened for the ability to promote gastrointestinal tract by at least one antibiotic targeting the differentiation and /or expansion of Treg cells , Th17 cells , bacterial composition . 40 Thl cells and/ or Th2 cells from precursor cells , e . g . naive T Adherence to Gastrointestinal Cells : The compositions cells . By way of example , naïve T cells can be cultured in can optionally be tested for the ability to adhere to gastro - the presence of candidate bacteria or supernatants obtained intestinal cells . A method for testing adherence to gastroin - from cultures of candidate bacteria , and numbers of Treg testinal cells is described in e . g . , U . S . Pat. No . 4 ,839 , 281 . cells , Th17 cells , Th1 cells and /or Th2 cells can be deter Identification of Immunomodulatory Bacteria : In some 45 mined using standard techniques, such as FACS analysis . embodiments , immunomodulatory bacteria are identified by Markers indicative of Treg cells include , for example , the presence of nucleic acid sequences that modulate spo - CD25 +CD1270 . Markers indicative of Th17 cells include , rulation . In particular , signature sporulation genes are highly for example , CXCR3 - CCR6 + . Markers indicative of Th1 conserved across members of distantly related genera cells include , for example , CD4 + , CXCR3 + , and CCR6 - . including Clostridium and Bacillus. Traditional approaches 50 Markers indicative of Th2 cells include , for example , CD4 + , of forward genetics have identified many , if not all, genes CCR4 + , and CXCR3 - , CCR6 . Other markers indicative of that are essential for sporulation ( spo ) . The developmental particular T cells subpopulations are known in the art, and program of sporulation is governed in part by the successive may be used in the assays described herein , e . g . , to identify action of four compartment -specific sigma factors (appear populations of immune cells impacted by candidate immu ing in the order of, oE , OG and oK ) , whose activities are 55 nomodulatory bacteria . Bacteria can be selected for inclu confined to the forespore ( oF and oG ) or the mother cell ( oE sion ( or exclusion ) in a microbial consortium based on the and oK ). In other embodiments , immunomodulatory bacte - ability to promote differentiation and /or expansion of a ria are identified by the biochemical activity of DPA pro desired immune cell subpopulation . ducing enzymes or by analyzing DPA content of cultures. As In other embodiments, immunomodulatory bacteria are part of the bacterial sporulation , large amounts of DPA are 60 identified by screening bacteria to determine whether the produced , and comprise 5 - 15 % of the mass of a spore . bacteria secrete short chain fatty acids (SCFA ) , such as, for Because not all viable spores germinate and grow under example , butyrate , acetate , propionate , or valerate , or com known media conditions, it is difficult to assess a total spore binations thereof. For example , secretion of short chain fatty count in a population of bacteria . As such , a measurement of acids into bacterial supernatants can be measured using DPA content highly correlates with spore content and is an 65 standard techniques . In one embodiment, bacterial superna appropriate measure for characterizing total spore content in tants can be screened to measure the level of one or more a bacterial population . short chain fatty acids using NMR , mass spectrometry ( e . g . , US 10 ,265 , 349 B2 37 38 GC -MS , tandem mass spectrometry, matrix -assisted laser In some embodiments , the composition comprises at least desorption / ionization , etc . ) , ELISA , or immunoblot. Expres one prebiotic . In one embodiment, the prebiotic is a carbo sion of bacterial genes responsible for production of short hydrate . In some embodiments , the composition comprises chain fatty acids can also be determined by standard tech - a prebiotic mixture, which comprises at least one carbohy niques , such as Northern blot , microarray , or quantitative 5 drate . A " carbohydrate ” refers to a sugar or polymer of PCR . sugars . The terms “ saccharide ," " polysaccharide , " " carbo Exemplary minimal microbial consortia : Minimal micro - hydrate , ” and “ oligosaccharide” can be used interchange bial consortia are shown herein in the Examples section and ably. Most carbohydrates are aldehydes or ketones with can prevent and /or treat existing symptoms of a food allergy . many hydroxyl groups , usually one on each carbon atom of These exemplary minimalmicrobial consortia should not be 10 the molecule . Carbohydrates generally have the molecular construed as limiting and are intended only for the better formula (CH , O ) n . A carbohydrate can be a monosaccharide , understanding of the methods and compositions described a disaccharide , trisaccharide, oligosaccharide , or polysac herein . charide . The most basic carbohydrate is a monosaccharide , In one embodiment, a minimal microbial consortium such as glucose , sucrose , galactose , mannose , ribose , arab consists essentially of : Clostridum ramosum , C . scindens, C . 15 inose , xylose , and fructose . Disaccharides are two joined hiranonsis , C . bifermentans, C . leptum and C . sardiniensis . monosaccharides . Exemplary disaccharides include sucrose , In one embodiment, a minimal microbial consortium maltose , cellobiose , and lactose . Typically, an oligosaccha consisting essentially of: Clostridum ramosum , C . scindens, ride includes between three and six monosaccharide units C . hiranonsis , C . bifermentans, C . leptum and C . sardinien - ( e . g ., raffinose , stachyose ) , and polysaccharides include six sis is used in the prevention and / or treatment of existing 20 or more monosaccharide units . Exemplary polysaccharides allergic reactions to food . include starch , glycogen , and cellulose . Carbohydrates can In one embodiment, a minimal microbial consortium contain modified saccharide units , such as 2 ' -deoxyribose consists essentially of: Bacteroides fragilis , B . thetaiotao wherein a hydroxyl group is removed , 2 - fluororibose micron , B . ovatus, Parabacteroides goldsteinii , and Pre - wherein a hydroxyl group is replace with a fluorine , or votella tannerae . 25 N -acetylglucosamine , a nitrogen - containing form of glucose In one embodiment, a minimal microbial consortium ( e . g . , 2 ' - fluororibose , deoxyribose , and hexose ) . Carbohy consisting essentially of: Bacteroides fragilis , B . thetaiotao drates can exist in many different forms, for example , micron , B . ovatus, Parabacteroides goldsteinii , and Pre conformers , cyclic forms, acyclic forms, stereoisomers , tau votella tannerae is used to treat existing allergic reactions to tomers , anomers, and isomers. Carbohydrates can be puri food . 30 fied from natural ( e . g . , plant or microbial) sources ( i. e ., they By “ consists essentially of in this context is meant that are enzymatically synthesized ) , or they can be chemically if the addition of another microbe does not improve the synthesized or modified . treatment or prevention of allergy as described and defined Suitable prebiotic carbohydrates can include one or more herein , that microbe is not essential to the protective or of a carbohydrate , carbohydrate monomer , carbohydrate therapeutic effect . 35 oligomer, or carbohydrate polymer. In certain embodiments , Prebiotics the pharmaceutical composition or dosage form comprises at A prebiotic is a selectively fermented ingredient that least one type of microbe and at least one type of non allows specific changes, both in the composition and /or digestible saccharide, which includes non -digestible mono activity in the gastrointestinal microbiota , that confers neu saccharides , non - digestible oligosaccharides, or non -digest tral or positive benefits upon host well- being and health . 40 ible polysaccharides. In one embodiment, the sugar units of Prebiotics can include complex carbohydrates , amino acids, an oligosaccharide or polysaccharide can be linked in a peptides, or other nutritional components useful for the single straight chain or can be a chain with one or more side survival , colonization and persistence of the bacterial com - branches. The length of the oligosaccharide or polysaccha position . Prebiotics include , but are not limited to , amino ride can vary from source to source . In one embodiment, acids , biotin , fructooligosaccharide, galactooligosaccha - 45 small amounts of glucose can also be contained in the chain . rides , inulin , lactulose ,mannan oligosaccharides, oligofruc - In another embodiment, the prebiotic composition can be tose - enriched inulin , oligofructose , oligodextrose , tagatose , partially hydrolyzed or contain individual sugar moieties trans - galactooligosaccharide , and xylooligosaccharides. that are components of the primary oligosaccharide ( see e . g ., Suitable prebiotics are usually plant- derived complex U . S . Pat. No . 8 ,486 ,668 ) . carbohydrates , oligosaccharides or polysaccharides . Gener - 50 Prebiotic carbohydrates can include , but are not limited to ally , prebiotics are indigestible or poorly digested by humans monosaccharides ( e . g . , trioses , tetroses , pentoses , aldopen and serve as a food source for bacteria . Prebiotics, which can toses , ketopentoses, hexoses, cyclic hemiacetals , ketohex be used in the pharmaceutical dosage forms, and pharma - oses, heptoses ) and multimers thereof, as well as epimers , ceutical compositions provided herein include, without limi- cyclic isomers, stereoisomers, and anomers thereof. Non tation , galactooligosaccharides (GOS ) , trans - galactooli - 55 limiting examples of monosaccharides include ( in either the gosaccharides , fructooligosaccharides or oligofructose L - or D - conformation ) glyceraldehyde , threose , ribose , ( FOS ) , inulin , oligofructose - enriched inulin , lactulose , ara altrose , glucose , mannose , talose , galactose , gulose , idose , binoxylan , xylooligosaccharides (XOS ), mannooligosaccha - lyxose , arabanose , xylose , allose , erythrose , erythrulose , rides , gum guar, gum Arabic , tagatose , amylose, amylopec - tagalose , sorbose , ribulose , psicose , xylulose , fructose , dihy tin , xylan , pectin , and the like and combinations of thereof. 60 droxyacetone , and cyclic (alpha or beta ) forms thereof. Prebiotics can be found in certain foods, e . g . , chicory root, Multimers (disaccharides , trisaccharides , oligosaccharides , Jerusalem artichoke , Dandelion greens, garlic , leek , onion , polysaccharides ) thereof include, but are not limited to , asparagus , wheat bran , wheat flour, banana , milk , yogurt, sucrose , lactose, maltose , lactulose , trehalose , cellobiose , sorghum , burdock , broccoli , Brussels sprouts , cabbage , cau - kojibiose , nigerose , isomaltose , sophorose , laminaribiose , liflower , collard greens , kale , radish and rutabaga , and miso . 65 gentioboise, turanose , maltulose , palatinose , gentiobiulose , Alternatively, prebiotics can be purified or chemically or mannobiose , melibiulose , rutinose , rutinulose , xylobiose , enzymatically synthesized . primeverose , amylose , amylopectin , starch ( including resis US 10 , 265 , 349 B2 39 40 tant starch ) , chitin , cellulose , agar, agarose , xylan , glycogen , saccharide at the reducing end is in fact a reducing sugar. bacterial polysaccharides such as capsular polysaccharides , Most oligosaccharides described herein are described with LPS , and peptidoglycan , and biofilm exopolysaccharide the name or abbreviation for the non -reducing saccharide ( e . g . , alginate , EPS ), N - linked glycans, and O - linked gly - ( e . g ., Gal or D -Gal ) , preceded or followed by the configu cans. Prebiotic sugars can be modified and carbohydrate 5 ration of the glycosidic bond (a or B ) , the ring bond , the ring derivatives include amino sugars ( e . g ., sialic acid , N - acetyl position of the reducing saccharide involved in the bond , and glucosamine, galactosamine ), deoxy sugars ( e. g ., rhamnose , then the name or abbreviation of the reducing saccharide fucose , deoxyribose ), sugar phosphates , glycosylamines , ( e. g. , Glc or D -Glc ). The linkage ( e. g. , glycosidic linkage , sugar alcohols , and acidic sugars ( e . g . , glucuronic acid , galactosidic linkage, glucosidic linkage ) between two sugar ascorbic acid ). 10 In one embodiment, the prebiotic carbohydrate compo units can be expressed , for example , as 1 , 4 , 1 - 4 , or ( 1 - 4 ) . nent of the pharmaceutical composition consists essentially Both FOS and GOS are non -digestible saccharides . B of one or more non - digestible saccharides . glycosidic linkages of saccharides , such as those found in , In one embodiment, the prebiotic carbohydrate compo but not limited to , FOS and GOS , make these prebiotics nent of the pharmaceutical composition allows the commen - is15 mainlymainly non -digestible digestible and unabsorbable in the stomach and sal colonic microbiota , comprising microorganisms associ small intestine a - linked GOS (a -GOS ) is also not hydro ated with a healthy - state microbiome or presenting a low lyzed by human salivary amylase , but can be used by risk of a patient developing an autoimmune or inflammatory Bifidobacterium bifidum and Clostridium butyricum ( Ya condition , to be regularly maintained . In one embodiment, mashita A . et al. , 2004 . J . Appl. Glycosci. 51 : 115 - 122 ). FOS the prebiotic carbohydrate allows the co - administered or 20 and GOS can pass through the small intestine and into the co - formulated microbe or microbes to engraft, grow , and /or large intestine ( colon ) mostly intact, exceptwhere commen be regularly maintained in a mammalian subject . In some sal microbes and microbes administered as part of a phar embodiments , the mammalian subject is a human subject, maceutical composition are able to metabolize the oligosac for example , a human subject having or suspected of having charides . a food allergy . 25 GOS ( also known as galacto - oligosaccharides , galactooli In some embodiments , the prebiotic favors the growth of gosaccharides , trans - oligosaccharide ( TOS ) , transgalacto an administered microbe , wherein the growth of the admin - oligosaccharide ( TGOS ) , and trans - galactooligosaccharide ) istered microbe and /or the fermentation of the administered are oligomers or polymers of galactose molecules ending prebiotic by the administered microbe slows or reduces the mainly with a glucose or sometimes ending with a galactose growth of a pathogen or pathobiont. For example , FOS , 30 molecule and have varying degree of polymerization ( gen neosugar, or inulin promotes the growth of acid - forming erally the DP is between 2 - 20 ) and type of linkages . In one bacteria in the colon such as bacteria belonging to the genus embodiment, GOS comprises galactose and glucose mol Lactobacillus or Bifidobacterium and Lactobacillus aci - ecules . In another embodiment, GOS comprises only galac dophilus and Bifidobacterium bifidus can play a role in tose molecules . In a further embodiment, GOS are galac reducing the number of pathogenic bacteria in the colon ( see 35 tose - containing oligosaccharides of the form of [ B - D -Gal e . g ., U . S . Pat . No . 8 ,486 ,668 ) . Other polymers , such as ( 1 - 6 ) ] n - B - D -Gal - ( 1 - 4 ) - D - Glc wherein n is 2 - 20 . In another various galactans , lactulose , and carbohydrate based gums, embodiment, GOS are galactose -containing oligosaccha such as psyllium , guar, carrageen , gellan , and konjac , are rides of the form Glc al- 4 - [ ß Gal 1 - 6 ) ] , where n = 2 - 20 . In also known to improve gastrointestinal (GI ) health . another embodiment, GOS are in the form of a - D -Glc In some embodiments , the prebiotic comprises one or 40 ( 1 -4 ) - [B - D -Gal - ( 1 -6 )- In where n = 2 -20 . Gal is a galactopy more of GOS, lactulose , raffinose , stachyose , lactosucrose , ranose unit and Glc ( or Glu ) is a glucopyranose unit . FOS ( i . e . , oligofructose or oligofructan ) , inulin , isomalto - In one embodiment, a prebiotic composition comprises a oligosaccharide, xylo - oligosaccharide , paratinose oligosac GOS- related compound . A GOS - related compound can have charide , transgalactosylated oligosaccharides ( . e ., transga the following properties : a ) a “ lactose ” moiety ; e . g ., GOS lacto - oligosaccharides ) , transgalactosylate disaccharides, 45 with a gal- glu moiety and any polymerization value or type soybean oligosaccharides ( i. e ., soyoligosaccharides ) , gen - of linkage ; or b ) be stimulatory to " lactose fermenting” tiooligosaccharides , glucooligosaccharides , pecticoligosac microbes in the human GI tract ; for example , raffinose charides, palatinose polycondensates, difructose anhydride (gal - fru - glu ) is a “ related ” GOS compound that is stimula III , sorbitol, maltitol, lactitol, polyols , polydextrose , reduced tory to both lactobacilli and bifidobacteria . paratinose, cellulose , B -glucose , B -galactose , B - fructose , 50 Linkages between the individual sugar units found in verbascose , galactinol , and B - glucan , guar gum , pectin , high , GOS and other oligosaccharides include B - ( 1 -6 ), B - ( 1 - 4 ), sodium alginate , and lambda carrageenan , or mixtures B - ( 1 - 3 ) and B - ( 1 - 2 ) linkages . In one embodiment, the admin thereof. The GOS may be a short -chain GOS, a long -chain istered oligosaccharides ( e. g ., GOS) are branched saccha GOS , or any combination thereof. The FOS can be a rides . In another embodiment, the administered oligosac short -chain FOS , a long - chain FOS , or any combination 55 charides ( e . g . , GOS ) are linear saccharides . thereof. Alpha -GOS (also called alpha -bond GOS or alpha - linked In some embodiments , the prebiotic composition com - GOS) are oligosaccharides having an alpha - galactopyrano prises two carbohydrate species ( non - limiting examples syl group . Alpha -GOS comprises at least one alpha glyco being a GOS and FOS ) in a mixture of at least 1 : 1 , at least sidic linkage between the saccharide units . Alpha -GOS are 2 : 1 , at least 5 : 1 , at least 9 : 1 , at least 10 : 1 , about 20 : 1 , or at 60 generally represented by a - (Gal ) , . ( n usually represents an least 20 : 1. integer of 2 to 10 ) or a -( Gal ) n . Glc ( n usually represents an In some embodiments , the prebiotic comprises a mixture integer of 1 to 9 ) . Examples include a mixture of a - galac of one or more non -digestible oligosaccharides , non - digest - tosylglucose , a - galactobiose , a - galactotriose , a - galactotet ible polysaccharides , free monosaccharides, non -digestible raose , and higher oligosaccharides . Additional non - limiting saccharides , starch , or non - starch polysaccharides. 65 examples include melibiose , manninootriose, raffinose , Oligosaccharides are generally considered to have a stachyose , and the like , which can be produced from beat , reducing end and a non - reducing end , whether or not the soybean oligosaccharide, and the like. US 10 , 265 , 349 B2

Commercially available and enzyme synthesized alpha - or carrageenan , and are preferably prepared from pectin or GOS products are also useful for the compositions described alginate . The acid oligosaccharides can be prepared by the herein . Synthesis of alpha -GOS with an enzyme is con - methods described in e . g ., WO 01 /60378 , which is hereby ducted utilizing the dehydration condensation reaction of incorporated by reference . The acid oligosaccharide is pref a - galactosidase with the use of galactose , galactose - con - 5 erably prepared from high methoxylated pectin , which is taining substance , or glucose as a substrate . The galactose - characterized by a degree of methoxylation above 50 % . As containing substance includes hydrolysates of galactose - used herein , “ degree ofmethoxylation " ( also referred to as containing substances, for example , a mixture of galactose DE or “ degree of esterification ” ) is intended to mean the and glucose obtained by allowing beta - galactosidase to act extent to which free carboxylic acid groups contained in the on lactose , and the like. Glucose can be mixed separately 10 polygalacturonic acid chain have been esterified ( e . g . by with galactose and be used as a substrate with a - galactosi - methylation ) . In some embodiments, the acid oligosaccha dase ( see e . g . , WO 02 / 18614 ) . Methods of preparing alpha - rides have a degree of methoxylation above about 10 % , GOS have been described (see e . g . , EP 514551 and above about 20 % , above about 50 % , above about 70 % . In EP2027863 ) . some embodiments , the acid oligosaccharides have a degree In one embodiment, a GOS composition comprises a 15 ofmethylation above about 10 % , above about 20 % , above mixture of saccharides that are alpha - GOS and saccharides about 50 % , above about 70 % . that are produced by transgalactosylation using B -galacto - The term neutral oligosaccharides as used in the present sidase . In another embodiment, GOS comprises alpha -GOS . invention refers to saccharides which have a degree of In another embodiment, alpha -GOS comprises a - (Gal ) , polymerization of monose units exceeding 2 , exceeding 3 , from 10 % to 100 % by weight. In one embodiment, GOS 20 exceeding 4 , or exceeding 10 , which are not or only partially comprises only saccharides that are produced by transga - digested in the intestine by the action of acids or digestive lactosylation using B - galactosidase . enzymes present in the human upper digestive tract ( small In one embodiment , the pharmaceutical composition intestine and stomach ) but which are fermented by the comprises , in addition to one ormore microbes , an oligosac - human intestinal flora and preferably lack acidic groups . The charide composition that is a mixture of oligosaccharides 25 neutral oligosaccharide is structurally (chemically ) different comprising 1 - 20 % by weight of disaccharides, 1 - 20 % by from the acid oligosaccharide . The term “ neutral oligosac weight tri - saccharides , 1 - 20 % by weight tetra - saccharides, charides ” , as used herein , refers to saccharides which have and 1 - 20 % by weight penta - saccharides. In another embodi - a degree of polymerization of the oligosaccharide below 60 ment, an oligosaccharide composition is a mixture of oli - monose units . The term “ monose units ” refers to units gosaccharides consisting essentially of 1 - 20 % by weight of 30 having a closed ring structure e . g . , the pyranose or furanose disaccharides , 1 - 20 % by weight tri -saccharides , 1 - 20 % by forms. In some embodiments , the neutral oligosaccharide weight tetra - saccharides , and 1 - 20 % by weight penta - sac - comprises at least 90 % or at least 95 % monose units selected charides. from the group consisting of mannose, arabinose , fructose , In one embodiment, a prebiotic composition is a mixture fucose , rhamnose, galactose , - D - galactopyranose , ribose , of oligosaccharides comprising 1 - 20 % by weight of saccha - 35 glucose , xylose and derivatives thereof, calculated on the rides with a degree of polymerization (DP ) of 1 - 3 , 1 - 20 % by total number of monose units contained therein . Suitable weight of saccharides with DP of 4 - 6 , 1 - 20 % by weight of neutral oligosaccharides are preferably fermented by the gut saccharides with DP of 7 - 9 , and 1 -20 % by weight of flora . Non -limiting examples of suitable neutral oligosac saccharides with DP of 10 - 12 , 1 - 20 % by weight of saccha - charides are cellobiose ( 4 - 0 - B - D - glucopyranosyl- D - glu rides with DP of 13 - 15 . 40 cose ), cellodextrins (( 4 - O -B - D -glucopyranosyl ) n -D - glu In another embodiment, a prebiotic composition com - cose ) , B -cyclo -dextrins (Cyclic molecules of a - 1 -4 - linked prises a mixture of oligosaccharides comprising 50 -55 % by D - glucose ; a - cyclodextrin -hexamer , B -cyclodextrin -hep weight of disaccharides, 20 - 30 % by weight trisaccharides , tamer and y -cyclodextrin - octamer ) , indigestible dextrin , 10 -20 % by weight tetra - saccharide, and 1 - 10 % by weight gentiooligosaccharides (mixture of B - 1 - 6 linked glucose penta - saccharides . In one embodiment, a GOS composition 45 residues, some 1 - 4 linkages ) , glucooligosaccharides (mix is a mixture of oligosaccharides comprising 52 % by weight ture of a - D - glucose ), isomaltooligosaccharides ( linear of disaccharides , 26 % by weight trisaccharides , 14 % by a - 1 -6 linked glucose residues with some 1 - 4 linkages ) , weight tetra -saccharide , and 5 % by weight penta -saccha isomaltose ( 6 - 0 - a - D - glucopyranosyl- D - glucose ) ; isomal rides. In another embodiment, a prebiotic composition com - triose ( 6 - O - a - D - glucopyranosyl- ( 1 - 6 ) - a - D - glucopyrano prises a mixture of oligosaccharides comprising 45 - 55 % by 50 syl- D - glucose ), panose (6 -0 - a - D - glucopyranosyl -( 1 -6 )- a weight tri - saccharides , 15 - 25 % by weight tetra - saccharides , D -glucopyranosyl - ( 1 - 4 ) - D - glucose ), leucrose ( 5 - 0 - C - D 1 - 10 % by weight penta - saccharides . glucopyranosyl - D - fructopyranoside) , palatinose or In certain embodiments , the composition comprises a isomaltulose (6 - O - a - D - glucopyranosyl- D - fructose ), thean mixture of neutral and acid oligosaccharides as disclosed in derose ( O - a - D - glucopyranosyl- ( 1 -6 ) - O - a - D - glucopyrano e . g . , WO 2005/ 039597 ( N . V . Nutricia ) and U . S . Patent 55 syl - ( 1 - 2 ) - B - D - fructo furanoside) , D - agatose , D - lyxo -hexy Application 20150004130 . In one embodiment, the acid lose , lactosucrose ( O - D - galactopyranosyl - ( 1 - 4 ) - O - a - D oligosaccharide has a degree of polymerization (DP ) glucopyranosyl- ( 1 - 2 ) - B - D - fructofuranoside ) , between 1 and 5000 . In another embodiment , the DP is a - galactooligosaccharides including raffinose , stachyose between 1 and 1000 . In another embodiment, the DP is and other soy oligosaccharides (O - a - D - galactopyranosyl between 2 and 250 . If a mixture of acid oligosaccharides 60 ( 1 - 6 ) - C - D - glucopyranosyl- B - D - fructofuranoside ) , B - galac with different degrees of polymerization is used , the average tooligosaccharides or transgalacto - oligosaccharides ( B - D DP of the acid oligosaccharide mixture is preferably galactopyranosyl - ( 1 - 6 ) - [ B - D - glucopyranosyl] n - ( 1 - 4 ) A - D between 2 and 1000 . The acid oligosaccharide can be a glucose ), lactulose (4 - 0 -B -D - galactopyranosyl- D - fructose ) , homogeneous or heterogeneous carbohydrate . The acid oli 4 - galatosyllactose (ß - D - galactopyranosyl- ( 1 - 4 ) - O - B - D - glu gosaccharides can be prepared from pectin , pectate , alginate , 65 copyranosyl- ( 1 -4 )- D - glucopyranose ), synthetic galactooli chondroitine , hyaluronic acids , heparin , heparane , bacterial gosaccharide (neogalactobiose , isogalactobiose, galsucrose , carbohydrates , sialoglycans, fucoidan , fucooligosaccharides isolactose I, II and III) , fructans- Levan -type (B - D -2( 6 ) US 10 , 265 , 349 B2 43 44 fructofuranosyl) n a - D - glucopyranoside) , fructans- Inulin dehydrogenase is hydrolyzed by a lactonase to yield D - xy type (B - D -( 2 - 1 )- fructofuranosyl ) n a - D -glucopyranoside ), lonic acid , and xylonate dehydratase activity then yields 1 f - b - fructofuranosylnystose (B - D - ( 2 - 1 ) - fructofurano 2 -keto - 3 - deoxy -xylonate . The final steps of the Weimberg syl) n B - D - fructofuranoside ), xylooligo - saccharides ( B - D pathway are a dehydratase reaction to form 2 -keto glutarate ( ( 1 > 4 ) -xylosen , lafinose , lactosucrose and arabinooli- 5 semialdehyde and an oxidizing reaction to form 2 -ketoglu gosaccharides. tarate , an intermediate of the Krebs cycle . In some embodiments , the neutral oligosaccharide is The Dahms pathway follows the same mechanism as the selected from the group consisting of fructans , fructooli Weimberg pathway but diverges once it has yielded 2 -keto gosaccharides , indigestible dextrins galactooligo -saccha - 3 -deoxy -xylonate . In the Dahms pathway, an aldolase splits rides ( including transgalactooligosaccharides) , xylooli - 10 2 -keto - 3 -deoxy -xylonate into pyruvate and glycolaldehyde . gosaccharides , arabinooligo -saccharides , The xylose oxido - reductase pathway , also known as the glucooligosaccharides, mannooligosaccharides, fucooli - xylose reductase -xylitol dehydrogenase pathway , begins by gosaccharides and mixtures thereof. the reduction of D - xylose to xylitol by xylose reductase Suitable oligosaccharides and their production methods followed by the oxidation of xylitol to D -xylulose by xylitol are further described in Laere K . J . M . (Laere , K . J. M ., 15 dehydrogenase . As in the isomerase pathway, the next step Degradation of structurally different non -digestible oli- in the oxido -reductase pathway is the phosphorylation of gosaccharides by intestinal bacteria : glycosylhydrolases of D -xylulose by xylulose kinase to yield D -xylolose -5 -phos Bi. adolescentis . PhD -thesis (2000 ) , Wageningen Agricul- phate . tural University , Wageningen , The Netherlands) , the entire Xylose is present in foods like fruits and vegetables and content of which is hereby incorporated by reference . Trans- 20 other plants such as trees for wood and pulp production . galactooligosaccharides ( TOS ) are for example sold under Thus , xylose can be obtained in the extracts of such plants. the trademark VivinalTM ( Borculo Domo Ingredients , Neth Xylose can be obtained from various plant sources using erlands ). Indigestible dextrin , which can be produced by known processes including acid hydrolysis followed by pyrolysis of corn starch , comprises a 1( 4 ) and a (16 ) various types of chromatography . Examples of such meth glucosidic bonds, as are present in the native starch , and 25 ods to produce xylose include those described in Maurelli , contains 1 2 and 1 3 linkages and levoglucosan . Due to L . et al. ( 2013 ) , Appl. Biochem . Biotechnol. 170 : 1104 - 1118 ; these structural characteristics , indigestible dextrin contains Hooi H . T et al. (2013 ) , Appl. Biochem . Biotechnol. 170 : well -developed , branched particles that are partially hydro - 1602 - 1613 ; Zhang H - J . et al. ( 2014 ) , Bioprocess Biosyst . lyzed by human digestive enzymes. Numerous other com - Eng . 37 : 2425 - 2436 . mercial sources of indigestible oligosaccharides are readily 30 Culture and Storage of Consortium Constituents available and known to skilled persons in the art . For For banking , the strains included in the bacterial compo example , transgalactooligosaccharide is available from sition can be ( 1 ) isolated directly from a specimen or taken Yakult Honsha Co . , Tokyo , Japan . Soybean oligosaccharide from a banked stock , (2 ) optionally cultured on a nutrient is available from Calpis Corporation distributed by Ajino agar or broth that supports growth to generate viable bio moto U . S . A . Inc . , Teaneck , N . J . 35 mass, and ( 3 ) the biomass optionally preserved in multiple In a further embodiment, the prebiotic mixture of the aliquots in long -term storage . pharmaceutical composition described herein comprises an In embodiments using a culturing step , the agar or broth acid oligosaccharide with a DP between 1 and 5000 , pre - contains nutrients that provide essential elements and spe pared from pectin , alginate, and mixtures thereof; and a cific factors that enable growth . An example would be a neutral oligosaccharide , selected from the group of fructans, 40 medium composed of 20 g /L glucose, 10 g /L yeast extract , ructooligosaccharides, indigestible dextrins , galactooli - 10 g / L soy peptone , 2 g / L citric acid , 1 . 5 g / L sodium gosaccharides including transgalacto - oligosaccharides, phosphate monobasic , 100 mg/ L ferric ammonium citrate , xylooligosaccharides, arabinooligosaccharides, glucooli 80 mg /L magnesium sulfate , 10 mg/ L hemin chloride , 2 gosaccharides , mannooligosaccharides, fucooligosaccha mg/ L calcium chloride, and 1 mg/ L menadione . A variety of rides , and mixtures thereof. 45 microbiological media and variations are well known in the In certain embodiments , the prebiotic mixture comprises art ( e . g . R . M . Atlas, Handbook of Microbiological Media xylose . In other embodiments , the prebiotic mixture com ( 2010 ) CRC Press ) . Medium can be added to the culture at prises a xylose polymer ( i . e . xylan ) . In some embodiments , the start , can be added during the culture , or can be inter the prebiotic comprises xylose derivatives , such as xylitol, a mittently continuously flowed through the culture . The sugar alcohol generated by reduction of xylose by catalytic 50 strains in the bacterial composition can be cultivated alone , hydrogenation of xylose , and also xylose oligomers (e . g ., as a subset of the bacterial composition , or as an entire xylooligosaccharide ) . While xylose can be digested by collection comprising the bacterial composition . As an humans, via xylosyltransferase activity, most xylose example , a first strain can be cultivated together with a ingested by humans is excreted in urine. In contrast, some second strain in a mixed continuous culture , at a dilution rate microorganisms are efficient at xylose metabolism or can be 55 lower than the maximum growth rate of either cell to prevent selected for enhanced xylose metabolism . Microbial xylose the culture from washing out of the cultivation . metabolism can occur by at least four pathways, including The inoculated culture is incubated under favorable con the isomerase pathway, the Weimburg pathway , the Dahms ditions for a time sufficient to build biomass . For bacterial pathway , and , for eukaryotic microorganisms, the oxido - compositions for human use this is often at normal body reductase pathway. 60 temperature ( 37° C . ) , pH , and other parameter with values The xylose isomerase pathway involves the direct con - similar to the normal human niche. The environment can be version of D -xylose into D -xylulose by xylose isomerase , actively controlled , passively controlled ( e . g . , via buffers ) , after which D - xylulose is phosphorylated by xylulose kinasease or allowed to drift . For example , for anaerobic bacterial to yield D -xylolose - 5 -phosphate , an intermediate of the compositions ( e . g ., gut microbiota ), an anoxic /reducing pentose phosphate pathway . 65 environment can be employed . This can be accomplished by In the Weimberg pathway, D - xylose is oxidized to D -xy - addition of reducing agents / factors such as cysteine to the lono -lactone by a D - xylose dehydrogenase . Then D - xylose broth , and /or stripping it ofoxygen . As an example , a culture US 10 , 265 , 349 B2 45 46 of a bacterial composition can be grown at 37° C . , pH 7 , in cultured separately and subsequently mixed together. In one the medium above , pre -reduced with 1 g / L cysteine .HC1 . embodiment, one or more of the populations of bacterial When the culture has generated sufficient biomass , it can cells in the composition are co - cultured . be preserved for banking or storage . The organisms can be Dosage , Administration and Formulations placed into a chemical milieu that protects from freezing 5 In some embodiments , cells over a range of, for example , (adding ‘ cryoprotectants ' ), drying (?lyoprotectants ') , and /or 2 -5x10 % , or more, e . g ., 1x10 “ , 1x107, 1x108 , 5x108, 1x109, osmotic shock ( osmoprotectants ' ) , dispensing into multiple 59, 1x1010 , 5x101° or more can be administered in a com position comprising a microbial consortium . The dosage ( optionally identical) containers to create a uniform bank , range for the bacteria depends upon the potency, and include and then treating the culture for preservation . Containers are amounts large enough to produce the desired effect, e . g . , generally impermeable and have closures that assure isola - 10 reduction in at least one symptom of a food allergy in a tion from the environment. Cryopreservation treatment is treated subject. The dosage should not be so large as to cause accomplished by freezing a liquid at ultra - low temperatures unacceptable adverse side effects . Generally , the dosage will ( e . g . , at or below - 80° C . ) . Dried preservation removes vary with the type of illness , and with the age, condition , and water from the culture by evaporation ( in the case of spray sex of the patient. The dosage can be determined by one of drying or ' cool drying ' ) or by sublimation ( e . g . , for freeze 15 skill in the art and can also be adjusted by the individual drying , spray freeze drying ) . Removal of water improves physician in the event of any complication . long - term bacterial composition storage stability at tempera For use in the various aspects described herein , an effec tures elevated above cryogenic . If the bacterial composition tive amount of cells in a composition as described herein comprises spore forming species and results in the produc - comprises at least 102 bacterial cells , at least 1x103 bacterial tion of spores , the final composition can be purified by 20 cells , at least 1x104 bacterial cells , at least 1x10 % bacterial additional means such as density gradient centrifugation cells, at least 1x106 bacterial cells, at least 1x107 bacterial preserved using the techniques described above . Bacterial cells , at least 1x108 bacterial cells , at least 1x10° bacterial composition banking can be done by culturing and preserv cells , at least 1x1010 bacterial cells , at least 1x1011 bacterial ing the strains individually , or by mixing the strains together cells , at least 1x10 ^ - bacterial cells or more . Where a to create a combined bank . As an example of cryopreserva - 255 microbial consortium is isolated and / or purified from a tion , a bacterial composition culture can be harvested by subject that is tolerant to a selected food allergen , the bacterial cells can be derived from one or more donors, or centrifugation to pellet the cells from the culture medium , can be obtained from an autologous source . In some embodi the supernate decanted and replaced with fresh culture broth ments of the aspects described herein , the cells of the containing 15 % glycerol. The culture can then be aliquoted microbial consortium are expanded or maintained in culture into 1 mL cryotubes , sealed , and placed at - 80° C . for 30 prior to administration to a subject in need thereof. In one long -term viability retention . This procedure achieves embodiment, the microbial consortium is obtained from a acceptable viability upon recovery from frozen storage . microbe bank . Members of a therapeutic or preventive / Organism production can be conducted using similar prophylactic consortium are generally administered culture steps to banking , including medium composition and together. e . g . , in a single admixture. However, it is specifi culture conditions. It can be conducted at larger scales of 35 cally contemplated herein that members of a given consor operation , especially for clinical development or commer tium can be administered as separate dosage forms or cial production . At larger scales , there can be several sub sub -mixtures or sub - combinations of the consortium mem cultivations of the bacterial composition prior to the final bers . Thus, for a consortium of e . g . , six members , the cultivation . At the end of cultivation , the culture is harvested consortium can be administered , for example , as a single to enable further formulation into a dosage form for admin - 40 preparation including all six members ( in one or more istration . This can involve concentration , removal of unde - dosage units , e . g ., one or more capsules ) or as two or more sirable medium components , and /or introduction into a separate preparations that , in sum , include all members of chemical milieu that preserves thebacterial composition and the given consortium . While administration as a single renders it acceptable for administration via the chosen route . admixture is preferred , a potential advantage of the use of For example , a bacterial composition can be cultivated to a 45 e . g . , individual units for each member of a consortium , is concentration of 1010 CFU /mL , then concentrated 20 - fold that the actual strains administered to any given subject can by tangential flow microfiltration ; the spent medium may be be tailored , if necessary , by selecting the appropriate com exchanged by diafiltering with a preservative medium con - bination of, for example , single species dosage units that sisting of 2 % gelatin , 100 mM trehalose , and 10 mM sodium together comprise the desired consortium . phosphate buffer. The suspension can then be freeze - dried to 50 Biomass of administered species , per dose , vs . known in a powder and titrated . vivo biomass : It is contemplated herein that the consortium After drying , the powder can be blended to an appropriate composition is formulated to deliver a larger biomass than potency , and mixed with other cultures and /or a filler such the normal biomass of the commensal organisms in a as microcrystalline cellulose for consistency and ease of “ healthy ” individual. For example , the range of biomasses handling , and the bacterial composition formulated as pro - 55 contemplated for delivery and colonization can be found in vided herein . Table 1 , column 2 , as compared to the normal biomass in a In one embodiment, a composition comprising a micro - healthy individual as shown in Table 1 , columns 3 & 4 . The bial consortium as described herein , is not a fecal transplant. table below shows the range of administered biomasses of In some embodiments all or essentially all of the bacterial organisms relative to published data at specific locations . entities present in a purified population are originally 60 Note , in many cases the bacterial quantitation in Gustafsson , obtained from a fecal material and subsequently , e . g . , for 1982 was to general categories of organisms , such as production of pharmaceutical compositions, are grown in Clostridia , and incorporated multiple species under those culture as described herein or otherwise known in the art . In headers . Individual species in the consortia would thus one embodiment, the bacterial cells are cultured from a likely be less than the actual highest reported biomass at the bacterial stock and purified as described herein . In one 65 specific locations ; the small and large intestinal biomass data embodiment, each of the populations of bacterial cells are should thus be considered an upper - bound for what might independently cultured and purified , e . g . , each population is occur in vivo in normal individuals . US 10 , 265 ,349 B2 48

Consortia Small Intestinal Large Intestinal Species Biomass Biomass Biomass Reference Bacteroides 1 x 107- < 103 CFU / g in 108 - 1011 CFU / g Gustafsson , fragilis 5 x 108 duodenum 1982 . [ 1 ] CFU /mL jejunum 103- 108 CFU / g in ileum B . 1 x 107 < 103 CFU / g in 108- 1011 CFU / g Gustafsson , thetaiotaomicron 5 x 108 duodenum 1982 . CFU /mL jejunum Bry, 1996 . [ 2 ] 103- 108 CFU / g in ileum B . ovatus 1 x 107- < 103 CFU / g in 108- 1011 CFU / g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 103 -108 CFU / g in ileum C . bifermentans 1 x 107 < 103 CFU /g in 0 - 106 CFU / g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 102- 104 CFU /g in ileum C . hiranonsis 1 x 107- < 103 CFU / g in 0 - 106 CFU / g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 102- 104 CFU / g in ileum C . leptum 1 x 107- < 103 CFU /g in 0 - 106 CFU /g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 102- 104 CFU / g in ileum Clostridium 1 x 107 < 103 CELCFU / g in 0 - 106 CFU /g Gustafsson , ramosum 5 x 108 duodenum 1982. CFU /mL jejunum 102 -104 CFU / g in ileum C . sardiniensis 1 x 107 < 103 CFU / g in 0 - 106 CFU / g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 102- 104 CFU / g in ileum C . scindens 1 x 107 < 103 CFU /g in 0 - 106 CFU / g Gustafsson , 5 x 108 duodenum 1982 . CFU /mL jejunum 102- 104 CFU / g in ileum Parabacteroides 1 x 107 < 103 CFU / g in 0 - 106 CFU / g Gustafsson , goldsteinii 5 x 108 duodenumduode 1982 . CFU /mL jejunum 103- 108 CFU / g in ileum Prevotella 1 x 107- < 103 CFU / g in 0 - 106 CFU / g Gustafsson , tannerae 5 x 108 duodenum 1982 . CFU /mL jejunum < 104 CFU / g in ileum References : 1 . Gustafsson , B E . The physiological importance of the colonic microflora . Scand J . Gastroenterol Suppl. 1982 , 77 : 117 - 31. 2 . Bry L , et al. A model of host- microbial interactions in an open mammalian ecosystem . Science . 1996 , 273 ( 5280 ): 1380 - 3 . A pharmaceutical composition comprising a microbial enteral formulation can be utilized as well . Also contem consortium can be administered by any method suitable for 55 plated herein are food items that are inoculated with a depositing in the gastrointestinal tract , preferably the colon , microbial consortium as described herein . Compositions can of a subject ( e . g ., human , mammal, animal, etc . ) . Examples also be treated or untreated fecal flora , entire ( or substan of routes of administration include rectal administration by tially entire ) microbiota , or partially , substantially or com colonoscopy , suppository , enema, upper endoscopy , or upper pletely isolated or purified fecal flora , and can be push enteroscopy . Additionally, intubation through the nose 60 lyophilized , freeze - dried or frozen , or processed into a or the mouth by nasogastric tube , nasoenteric tube , or nasal powder. jejunal tube can be utilized . Oral administration by a solid In some embodiments , the compositions described herein such as a pill, tablet, a suspension , a gel, a geltab , a can be administered in a form containing one or more semisolid , a tablet , a sachet, a lozenge or a capsule or pharmaceutically acceptable carriers . Suitable carriers are microcapsule , or as an enteral formulation , or re - formulated 65 well known in the art and vary with the desired form and for final delivery as a liquid , a suspension , a gel, a geltab , a mode of administration of the composition . For example , semisolid , a tablet, a sachet , a lozenge or a capsule , or as an pharmaceutically acceptable carriers can include diluents or US 10 , 265 , 349 B2 49 50 excipients such as fillers, binders , wetting agents, disinte In one embodiment, a microbial consortium as described grators, surface - active agents , glidants , lubricants , and the herein is formulated with an enteric coating . An enteric like. Typically , the carrier may be a solid (including pow - coating can control the location of where a microbial con der ) , liquid , or combinations thereof. Each carrier is pref sortium is released in the digestive system . Thus, an enteric erably " acceptable " in the sense of being compatible with 5 coating can be used such that a microbial consortium the other ingredients in the composition and not injurious to containing composition does not dissolve and release the the subject. The carrier may be biologically acceptable and microbes in the stomach , which can be a toxic environment inert ( e . g ., it permits the composition to maintain viability of for many microbes , but rather travels to the small intestine , the biological material until delivered to the appropriate where it dissolves and releases the microbes in an environ site ) . 10 ment where they can survive . An enteric coating can be Oral compositions can include an inert diluent or an stable at low pH (such as in the stomach ) and can dissolve edible carrier. For the purpose of oral therapeutic adminis at higher pH ( for example , in the small intestine ) . Material tration , the active compound can be incorporated with that can be used in enteric coatings includes , for example , excipients and used in the form of tablets , lozenges , pas - alginic acid , cellulose acetate phthalate, plastics , waxes , tilles, troches , or capsules , e . g . , gelatin capsules . Oral com - 15 shellac , and fatty acids ( e . g . , stearic acid , palmitic acid ) . positions can also be prepared by combining a composition Enteric coatings are described , for example , in U . S . Pat. of the present disclosure with a food . In one embodiment a Nos . 5 ,225 , 202 , 5 , 733 ,575 , 6 , 139 , 875 , 6 ,420 ,473 , 6 , 455 , food used for administration is chilled , for instance , iced 052, and 6 , 569 ,457 , all of which are herein incorporated by flavored water. In certain embodiments , the food item is not reference in their entirety . The enteric coating can be an a potentially allergenic food item ( e . g ., not soy , wheat, 20 aqueous enteric coating . Examples of polymers that can be peanut , tree nuts , dairy , eggs , shellfish or fish ). Pharmaceu - used in enteric coatings include , for example , shellac (trade tically compatible binding agents , and/ or adjuvant materials name EmCoat 120 N , Marcoat 125 ) ; cellulose acetate phtha can be included as part of the composition . The tablets , pills , late ( trade names AQUACOAT , AQUACOAT ECD , SEPI capsules , troches and the like can contain any of the fol - FILMTM , KLUCELTM , and METOLOSETM ) ; polyvinylac lowing ingredients , or compounds of a similar nature : a 25 etate phthalate ( trade name SURETERICTM ) ; and binder such as microcrystalline cellulose , gum tragacanth or methacrylic acid ( trade name EUDRAGITTM ) . gelatin ; an excipient such as starch or lactose , a disintegrat- In one embodiment, an enteric coated probiotic compo ing agent such as alginic acid , primogel, or corn starch ; a sition comprising members of a microbial consortium as lubricant such as magnesium stearate or sterotes ; a glidant described herein is administered to a subject . In another such as colloidal silicon dioxide ; a sweetening agent such as 30 embodiment, an enteric coated probiotic and prebiotic com sucrose or saccharin ; or a flavoring agent such as pepper - position is administered to a subject. mint, methyl salicylate, orange flavoring, or other suitable Formulations suitable for rectal administration include flavorings . These are for purposes of example only and are gels , creams, lotions , aqueous or oily suspensions, dispers not intended to be limiting . ible powders or granules , emulsions , dissolvable solid mate The compositions comprising a microbial consortium can 35 rials , douches , and the like. The formulations are preferably also be prepared in the form of suppositories ( e . g . , with provided as unit -dose suppositories comprising the active conventional suppository bases such as cocoa butter and ingredient in one or more solid carriers forming the sup other glycerides ) or retention enemas for rectal delivery . The pository base , for example , cocoa butter. Suitable carriers for compositions can be prepared with carriers that will protect such formulations include petroleum jelly, lanolin , polyeth the consortium against rapid elimination from the body, such 40 yleneglycols , alcohols , and combinations thereof. Alterna as a controlled release formulation , including implants . tively , colonic washes with the rapid recolonization deploy Biodegradable , biocompatible polymers can be used , such as ment agent of the present disclosure can be formulated for ethylene vinyl acetate , polyanhydrides, polyglycolic acid , colonic or rectal administration . collagen , polyorthoesters , and polylactic acid . Such formu- Formulations suitable for oral administration may be lations can be prepared using standard techniques . The 45 provided as discrete units , such as tablets , capsules , cachets , materials can also be obtained commercially from , for syrups , elixirs , prepared food items, microemulsions, solu instance, Alza Corporation and Nova Pharmaceuticals , Inc . tions, suspensions, lozenges , or gel -coated ampules, each Liposomal suspensions can also be used as pharmaceutically containing a predetermined amount of the active compound ; acceptable carriers . These can be prepared according to as powders or granules ; as solutions or suspensions in methods known to those skilled in the art. 50 aqueous or non -aqueous liquids ; or as oil - in -water or water In some embodiments , a composition can be encapsulated in -oil emulsions. ( e . g . , enteric - coated formulations ). For instance , when the In some embodiments, the microbial consortium can be composition is to be administered orally , the dosage form is formulated in a food item . Some non - limiting examples of formulated so the composition is not exposed to conditions food items to be used with the methods and compositions prevalent in the gastrointestinal tract before the small intes - 55 described herein include : popsicles, cheeses , creams, choco tine, e . g . , high acidity and digestive enzymes present in the lates , milk , meat, drinks, yogurt , pickled vegetables , kefir , stomach . The encapsulation of compositions for therapeutic miso , sauerkraut, etc . In other embodiments , the food items use is routine in the art. Encapsulation can include hard can be juices , refreshing beverages, tea beverages, drink shelled capsules , which can be used for dry, powdered preparations, jelly beverages, and functional beverages ; ingredients soft - shelled capsules. Capsules can be made 60 alcoholic beverages such as beers ; carbohydrate -containing from aqueous solutions of gelling agents such as animal foods such as rice food products , noodles, breads , and protein ( e .g ., gelatin ), plant polysaccharides or derivatives pastas; paste products such as fish , hams, sausages, paste like carrageenans and modified forms of starch and cellu products of seafood ; retort pouch products such as curries , lose . Other ingredients can be added to a gelling agent food dressed with a thick starchy sauce , and Chinese soups ; solution such as plasticizers ( e . g ., glycerin and or sorbitol) , 65 soups ; dairy products such as milk , dairy beverages , ice coloring agents , preservatives , disintegrants , lubricants and creams, cheeses , and yogurts ; fermented products such as surface treatment . fermented soybean pastes, fermented beverages , and pick US 10 , 265, 349 B2 51 52 les; bean products ; various confectionery products including and nonessential amino acids, carbohydrates, lipids, food biscuits , cookies, and the like , candies, chewing gums, stuffs , dietary supplements , short chain fatty acids and the gummies, cold desserts including jellies , cream caramels , like . Preferred compositions comprise vitamins and / or min and frozen desserts ; instant foods such as instant soups and erals in any combination . Vitamins for use in a composition instant soy - bean soups ; and the like . It is preferred that food 5 as described herein can include vitamins B , C , D , E , folic preparations not require cooking after admixture with the acid , K , niacin , and like vitamins . The composition can microbial consortium to avoid killing the microbes . contain any or a variety of vitamins as may be deemed useful Formulations of a microbial consortium can be prepared for a particularly application , and therefore, the vitamin by any suitable method , typically by uniformly and inti - content is not to be construed as limiting. Typical vitamins mately admixing the consortium with liquids or finely 10 are those , for example , recommended for daily consumption divided solid carriers or both , in the required proportions and and in the recommended daily amount (RDA ) , although then , if necessary, shaping the resulting in mixture into the precise amounts can vary . The composition can preferably desired shape . In addition , the microbial consortium can be include a complex of the RDA vitamins, minerals and trace treated to prolong shelf - life , preferably the shelf - life of the minerals as well as those nutrients that have no established pre -determined gut flora will be extended via freeze drying . 15 RDA , but have a beneficial role in healthy human or In some embodiments , the microbial consortium as mammal physiology . The preferred mineral format would described herein is combined with one or more additional include those that are in either the gluconate or citrate form probiotic organisms prior to treatment of a subject. As used because these forms are more readily metabolized by lactic herein , the term “ probiotic ” refers to microorganisms that acid bacteria . In a related embodiment, the compositions form at least a part of the transient or endogenous flora or 20 described herein are contemplated to comprise a microbial microbial consortium and thereby exhibit a beneficial pro consortium in combination with a viable lactic acid bacteria phylactic and / or therapeutic effect on the host organism . in combination with any material to be adsorbed , including Probiotics are generally known to be clinically safe (i . e ., but not limited to nutrient supplements , foodstuffs , vitamins , non - pathogenic ) by those individuals skilled in the art. minerals , medicines , therapeutic compositions , antibiotics , Typical lactic acid -producing bacteria useful as a probiotic 25 hormones , steroids , and the like compounds where it is of this invention are efficient lactic acid producers which desirable to insure efficient and healthy absorption of mate include non - pathogenic members of the Bacillus genus rials from the gastrointestinal tract into the blood . The which produce bacteriocins or other compounds which amount of material included in the composition can vary inhibit the growth of pathogenic organisms. widely depending upon the material and the intended pur Exemplary lactic acid - producing , non -pathogenic Bacil - 30 pose for its absorption , such that the composition is not to be lus species include , but are not limited to : Bacillus coagu - considered as limiting . lans ; Bacillus coagulans Hammer; and Bacillus brevis sub - In some embodiments , the compositions described herein species coagulans. can further include a prebiotic and /or a fiber .Many forms of Exemplary lactic acid -producing Lactobacillus species “ fiber ” exhibit some level of prebiotic effect. Thus , there is include , but are not limited to : Lactobacillus acidophilus, 35 considerable overlap between substances that can be clas Lactobacillus casei, Lactobacillus DDS - 1 , Lactobacillus sified as " prebiotics ” and those that can be classified as GG , Lactobacillus rhamnosus, Lactobacillus plantarum , “ fibers ” . Non - limiting examples of prebiotics suitable for Lactobacillus reuteri , Lactobacillus gasserii, Lactobacillus use in the compositions and methods include psyllium , jensenii , Lactobacillus delbruekii , Lactobacillus, bulgari- fructo -oligosaccharides , inulin , oligofructose , galacto -oli cus, Lactobacillus salivarius and Lactobacillus sporogenes 40 gosaccharides , isomalto - oligosaccharides xylo -oligosaccha (also designated as Bacillus coagulans ) . Exemplary lactic rides, soy -oligosaccharides , gluco -oligosaccharides , man acid - producing Sporolactobacillus species include all nan - oligosaccharides , arabinogalactan , arabinxylan , lacto Sporolactobacillus species, for example, Sporolactobacillus sucrose, gluconannan , lactulose, polydextrose , oligodextran , P44 . gentioligosaccharide, pectic oligosaccharide , xanthan gum , Exemplary lactic acid -producing Bifidiobacterium spe - 45 gum arabic , hemicellulose , resistant starch and its deriva cies include, but are not limited to : Bifidiobacterium ado - tives , and mixtures and / or combinations thereof . The com lescentis , Bifidiobacterium animalis , Bifidiobacterium bifi - positions can comprise from about 100 mg to about 100 g , dum , Bifidiobacterium bifidus, Bifidiobacterium breve , alternatively from about 500 mg to about 50 g , and alter Bifidiobacterium infantis , Bifidiobacterium infantus, Bifid - natively from about 1 g to about 40 g, of prebiotic , per day iobacterium longum , and any genetic variants thereof. 50 or on a less than daily schedule . Examples of suitable non - lactic acid - producing Bacillus Aspects of the technology described herein also include include , but are not limited to : Bacillus subtilis, Bacillus short chain fatty acids ( SCFAs) and medium chain triglyc uniflagellatus, Bacillus lateropsorus, Bacillus laterosporus erides (MCTS ). Short chain fatty acids can have immuno BOD , Bacillus megaterium , Bacillus polymyxa , Bacillus modulatory (i . e ., immunosuppressive ) effects and therefore licheniformis , Bacillus pumilus , and Bacillus sterothermo - 55 their production ( i . e . , biosynthesis or conversion by fermen philus . Other strains that could be employed due to probiotic tation ) is advantageous for the prevention , control, mitiga activity include members of the Streptococcus ( Enterococ - tion , and treatment of autoimmune and /or inflammatory cus ) genus. For example , Enterococcus faecium , is com - disorders (Lara - Villoslada F . et al. , 2006 . Eur J Nutr. 45 ( 7 ) : monly used as a livestock probiotic and , thus, could be 418 - 425 ) . In germ - free mice and vancomycin -treated con utilized as a co -administration agent. Furthermore , it is also 60 ventionalmice , administration of SCFA (acetate , propionate , intended that any of the acid -producing species of probiotic or butyrate ) restored normal numbers of Tregs in the large or nutritional bacteria known in the art can be used in the intestine (Smith P M , et al. Science . 2013 ; 569 -573 ). Short compositions comprising a microbial consortium as chain fatty acids ( SCFA ) are produced by some bacteria as described herein . a byproduct of xylose fermentation . SCFA are one of the A nutrient supplement comprising the microbial consor- 65 most abundantmetabolites produced by the gutmicrobiome , tium as described herein can include any of a variety of particularly the family Clostridiaceae , including members of nutritional agents , including vitamins, minerals , essential the genus Clostridium , Ruminococcus, or Blautia . In some US 10 , 265 , 349 B2 53 54 aspects , the pharmaceutical composition , dosage form , or kit micron , B . ovatus , Parabacteroides goldsteinii , and Pre comprises at least one type of microbe ( e. g . , one or more votella tannerae . In another embodiment, the kits comprise microbial species, such as a bacterial species , or more than at least four strains selected from the group consisting of: one strain of a particular microbial species ) and at least one Clostridium ramosum , C . scindens, C . hiranonsis, C . bifer type of prebiotic such that the composition , dosage form , or 5 mentans, C . leptum , and C . sardiniensis. In another embodi kit is capable of increasing the level of one or more immunomodulatory SCFA ( e. g ., acetate , propionate , ment, the kits comprise at least four strains selected from the butyrate , or valerate ) in a mammalian subject. Optionally, group consisting of: Bacteroides fragilis , B . thetaiotaomi the pharmaceutical composition , dosage form , or kit further cron , B . ovatus, Parabacteroides goldsteinii , and Prevotella comprises one or more substrates of one or more SCFA - 10 tannerae . In one embodiment, the kits comprise Bacteroides producing fermentation and / or biosynthesis pathways . In thetaiotaomicron or Bacteroides fragilis and at least one of certain embodiments , the administration of the composition , a strain selected from the group consisting of: Clostridium dosage form , or kit to a mammalian subject results in the ramosum , Clostridium scindens, Clostridium hiranonsis , increase of one or more SCFAs in the mammalian subject by Clostridium bifermentans , Clostridium leptum , Clostridium approximately 1 . 5 - fold , 2 - fold , 5 - fold , 10 - fold , 20 - fold , 15 Sardiniensis , Bacteroides ovatus, Parábacteroides gold 50 - fold , 100 -fold , or greater than 100 - fold . In some embodi steinii, Prevotella tannerae, Clostridum hathewayi , Clostri ments , the dysbiosis is caused byva a deficiency inin microbesmicrobes dum nexile , Clostridium hylemonae, Clostridium glycyr that produce short chain fatty acids. Accordingly , in some rhizinilyticum , Clostridium scindens, Clostridium lavalense , embodiments , the probiotic composition can contain a spe Clostridum fimetarium , Clostridium symbiosum , cies of bacteria that produce short chain fatty acids. 20 Clostridium sporosphaeroides, Dialister proprionicfaceins, MCTs passively diffuse from the GI tract to the portal Dialister succinatiphilus, Parabacteroides distasonis , Para system ( longer fatty acids are absorbed into the lymphatic bacteroides goldsteinii, Parabacteroides merdae , Pepto system ) without requirement for modification like long - streptococcus anaerobius, Subdoligranulum variabile , and chain fatty acids or very -long -chain fatty acids. In addition , Veilonella ratti . In one embodiment, the kits comprise MCTs do not require bile salts for digestion . Patients who 25 Bacteroides thetaiotaomicron or Bacteroides fragilis and at have malnutrition or malabsorption syndromes are treated least one of a strain selected from the group consisting of: with MCTs because they do not require energy for absorp - Clostridium ramosum , Clostridium scindens, Clostridium tion , use , or storage . Medium - chain triglycerides are gener - hiranonsis , Clostridium bifermentans , Clostridium leptum , ally considered a good biologically inert source of energy Clostridium sardiniensis , Clostridum hathewayi , Clostridum that the human body finds reasonably easy to metabolize . 30 nexile, Clostridium hylemonae , Clostridium glycyrrhizini They have potentially beneficial attributes in protein lyticum , Clostridium scindens , Clostridium lavalense , metabolism , but may be contraindicated in some situations Clostridum fimetarium , Clostridium symbiosum , and due to their tendency to induce ketogenesis and metabolic Clostridium sporosphaeroides . In another embodiment , the acidosis . Due to their ability to be absorbed rapidly by the kit comprises at least one reducing agent such as N - acetyl body , medium - chain triglycerides have found use in the 35 cysteine , cysteine , or methylene blue for growing , maintain treatment of a variety of malabsorption ailments . MCT ing and /or encapsulating the microbes under anaerobic con supplementation with a low - fat diet has been described as ditions. The kits described herein are also contemplated to the cornerstone of treatment for primary intestinal lymp - include cell growth media and supplements necessary for hangiectasia (Waldmann ' s disease ). MCTs are an ingredient expanding the microbial preparation . The kits described in parenteral nutritional emulsions . 40 herein are also contemplated to include one or more prebi Also contemplated herein are kits comprising , at a mini- otics as described herein . mum , a microbial consortium prep or formulations compris Prior to administration of the bacterial composition , the ing all of the members of the consortium in an admixture or patient may optionally have a pretreatment protocol to comprising all of the members of the consortium in sub - prepare the gastrointestinal tract to receive the bacterial combinations or sub -mixtures . In some embodiments , the kit 45 composition . In certain embodiments , the pretreatment pro further comprises empty capsules to be filled by the practi - tocol is advisable , such as when a patient has an acute tioner and /or one or more reagents for enteric coating such infection with a highly resilient pathogen . In other embodi capsules . It is also contemplated herein that the microbe ments , the pretreatment protocol is entirely optional, such as preparation is provided in a dried , lyophilized or powdered when the pathogen causing the infection is not resilient, or form . In one embodiment, the kits comprise at least 4 strains 50 the patient has had an acute infection that has been success selected from the group consisting of: Clostridium ramo - fully treated but where the physician is concerned that the sum , Clostridium scindens, Clostridium hiranonsis , infection may recur. In these instances, the pretreatment Clostridium bifermentans, Clostridium leptum , Clostridium protocol can enhance the ability of the bacterial composition sardiniensis , Bacteroides fragilis , Bacteroides thetaiotaomi- to affect the patient' s microbiome. In an alternative embodi cron , Bacteroides ovatus, Parabacteroides goldsteinii , Pre - 55 ment, the subject is not pre - treated with an antibiotic . votella tannerae , Clostridum hathewayi, Clostridum nexile , As one way of preparing the patient for administration of Clostridium hylemonae , Clostridium glycyrrhizinilyticum , the microbial ecosystem , at least one antibiotic can be Clostridium scindens, Clostridium lavalense , Clostridum administered to alter the bacteria in the patient. As another fimetarium , Clostridium symbiosum , Clostridium spo - way of preparing the patient for administration of the rosphaeroides, Dialister proprionicfaceins, Dialister succi- 60 microbial ecosystem , a standard colon - cleansing preparation natiphilus , Parabacteroides distasonis, Parabacteroides can be administered to the patient to substantially empty the goldsteinii, Parabacteroides merdae, Peptostreptococcus contents of the colon , such as used to prepare a patient for anaerobius, Subdoligranulum variabile, and Veilonella ratti. a colonoscopy. By “ substantially emptying the contents of In another embodiment, the kits comprise at least four the colon , ” this application means removing at least 75 % , at strains selected from the group consisting of: Clostridium 65 least 80 % , at least 90 % , at least 95 % , or about 100 % of the ramosum , C . scindens , C . hiranonsis , C . bifermentans, C . contents of the ordinary volume of colon contents . Antibi leptum , C . sardiniensis , Bacteroides fragilis , B . thetaiotao otic treatment can precede the colon - cleansing protocol. US 10 , 265, 349 B2 55 56 If a patient has received an antibiotic for treatment of an (MMCP - 1) and ( vi ) increase in Th2 cell skewing . Thus, infection , or if a patient has received an antibiotic as part of efficacious treatment and/ or prevention of food allergy using a specific pretreatment protocol, in one embodiment the the methods and compositions described herein can reduce antibiotic should be stopped in sufficient time to allow the or eliminate at least one of the symptoms or indicators antibiotic to be substantially reduced in concentration in the 5 associated with food allergy, as described above . “ Reduced ” gut before the bacterial composition is administered . In one symptoms or indicators mean at least 20 % reduced , at least embodiment, the antibiotic may be discontinued 1 , 2 , or 3 30 % reduced , at least 40 % reduced , at least 50 % reduced , at days before the administration of the bacterial composition . In one embodiment, the antibiotic can be discontinued 3 , 4 , least 60 % reduced , at least 70 % reduced , at least 80 % 5 , 6 , or 7 antibiotic half- lives before administration of the 10 reduced , at least 90 % reduced , at least 95 % reduced , at least bacterial composition . If the pretreatment protocol is part of 98 % reduced or even at least 99 % or further reduction . treatment of an acute infection , the antibiotic may be chosen Methods for the measurement of each of these parameters so that the infection is sensitive to the antibiotic, but the are known to those of ordinary skill in the art. constituents in the bacterial composition are not sensitive to The methods and compositions described herein provide the antibiotic . 15 treatment or prevention of food allergy involving or pro Any of the preparations described herein can be admin voking anaphylaxis — i . e . , IgE -mediated histamine release or istered once on a single occasion or on multiple occasions, direct allergen -mediated degranulation of mast cells and such as once a day for several days or more than once a day basophils and resulting pathology . Non - limiting examples on the day of administration ( including twice daily , three include allergy or anaphylactic reaction to peanut, tree nuts , times daily , or up to five times daily ). Or the preparation can 20 and shellfish , among others noted elsewhere herein . Food be administered intermittently according to a set schedule , sensitivity , e . g . , lactose intolerance or gluten intolerance e . g . , once weekly , once monthly , or when the patient involves differentmechanisms . While it is contemplated that relapses from the primary illness . In another embodiment, a microbial consortium as described herein can benefit those the preparation can be administered on a long -term basis to with food sensitivities ( e . g ., by reducing or eliminating a assure the maintenance of a protective or therapeutic effect. 25 dysbiotic state and thereby reducing gut inflammation ) , the In one embodiment, a first microbial consortium com - distinction between food sensitivities and food allergies prising at least one bacterial species known to enhance should be specifically noted . First and foremost , sensitivities colonization of beneficial organisms ( e . g . , Bacteroides do not provoke an anaphylactic response . thetaiotaomicron ) is administered to a subject prior to Effective prevention of food allergy can be assessed using administration of a second microbial consortium . 30 an accepted animal model, such as that described herein or Another aspect described herein relates to a method for others known to those of ordinary skill in the art , wherein a enhancing the colonization and /or persistence of a microbial regimen that sensitizes the animals to a given food allergen consortium , the method comprising administering a first in the absence of microbial consortium treatment fails to microbial consortium comprising at least 4 bacterial strains provoke a substantial allergic response in animals adminis selected from the group consisting of: Bacteroides fragilis , 35 tered a protective microbial consortium as described herein . B . thetaiotaomicron , B . ovatus, Parabacteroides goldsteinii, As used herein , the term " fails to provoke a substantial and Prevotella tannerae , to a subject prior to administering allergic response ” means that there is less than 20 % of the a second microbial consortium comprising at least 4 bacte - allergic response ( as measured by one or more of the criteria rial strains selected from the group consisting of: ( i) - ( vi ) described above ) seen in animals sensitized to the Clostridium ramosum , C . scindens, C . hiranonsis , C . bifer - 40 allergen but without administration of a protective or thera mentans , C . leptum and C . sardiniensis, wherein the first peutic microbial consortium as described herein . In human microbial consortium enhances the colonization and /or per - clinical practice , prevention or cure can be evaluated by sistence of the second microbial consortium . administration of the given microbial consortium followed It is also contemplated herein that a first microbial con by administration of an allergen under controlled circum sortium comprising at least 4 bacterial strains selected from 45 stances in a doctor ' s office or hospital setting . For preven the group consisting of: Clostridium ramosum , C . scindens, tion , the microbial consortium can be administered prior to C . hiranonsis , C . bifermentans, C . leptum and C . sardinien - a patient' s initial exposure to or consumption of a given food sis , is administered to a subject prior to administering a allergen . For therapy for established food allergy , the micro second microbial consortium comprising at least 4 bacterial bial consortium can be administered as described herein , strains selected from the group consisting of: Bacteroides 50 followed by consumption of the food allergen in a controlled fragilis , B . thetaiotaomicron , B . ovatus, Parabacteroides clinical setting . A lack of allergic reaction , or even a reduced goldsteinii , and Prevotella tannerae . allergic reaction relative to the patient' s previous allergic It is also contemplated herein that a first microbial con responses to the allergen ( i . e . , at least 20 % reduced , at least sortium comprising at least 4 bacterial strains selected from 30 % reduced , at least 40 % reduced , at least 50 % reduced , at the group consisting of: Clostridium ramosum , C . scindens, 55 least 60 % reduced , at least 70 % reduced , at least 80 % C . hiranonsis, C . bifermentans , C . leptum and C . sardinien - reduced , at least 90 % reduced , at least 95 % reduced , at least sis , is administered to a subject in combination with ( e . g ., 98 % reduced or even at least 99 % or further reduction ) is simultaneously ) a second microbial consortium comprising evidence of effective treatment. at least 4 bacterial strains selected from the group consisting Repeated administration of the microbial consortium may of : Bacteroides fragilis , B . thetaiotaomicron , B . ovatus , 60 be beneficial to maintain a protective or curative effect. Parabacteroides goldsteinii , and Prevotella tannerae . In addition , efficacy of a particular formulation can be Efficacy determined in vitro or in an in vivo or in situ mouse model Typically , a food allergy response can manifest with one as described in herein or as known in the art ( e . g . , Noval of more of the following symptoms or indicators : ( i ) a Rivas et al. J Allergy Clin Immunol (2013 ) 131( 1 ) : 201 - 212 marked drop in core body temperature, ( ii ) an increase in 65 or Noval Rivas et al. , Immunity (2015 ) 42 :512 - 523 , the total IgE , ( iii) an increase in allergen -specific IgE , ( iv ) mast contents of which are each incorporated herein in their cell expansion , ( v ) release of mast cell granule protease 1 entirety ) . US 10 , 265 , 349 B2 57 58 The singular terms “ a ," " an ,” and “ the” include plural the relevant art will recognize. For example , while method referents unless context clearly indicates otherwise . Simi steps or functions are presented in a given order, alternative larly , the word “ or” is intended to include " and " unless the embodiments may perform functions in a different order , or context clearly indicates otherwise . Although methods and functions may be performed substantially concurrently . The materials similar or equivalent to those described herein can 5 teachings of the disclosure provided herein can be applied to be used in the practice or testing of this disclosure , suitable other procedures or methods as appropriate . The various methods and materials are described below . The abbrevia - embodiments described herein can be combined to provide tion , “ e . g . ” is derived from the Latin exempli gratia , and is further embodiments . Aspects of the disclosure can be used herein to indicate a non - limiting example . Thus , the modified , if necessary , to employ the compositions, func abbreviation “ e . g " is synonymous with the term “ for 10 tions and concepts of the above references and application to example . ” provide yet further embodiments of the disclosure . More Definitions of common terms in cell biology and molecu over, due to biological functional equivalency consider lar biology can be found in “ The Merck Manual of Diag - ations , some changes can be made in protein structure nosis and Therapy ” , 19th Edition , published by Merck without affecting the biological or chemical action in kind or Research Laboratories , 2006 (ISBN 0 -911910 - 19 - 0 ) ; Robert 15 amount. These and other changes can be made to the S . Porter et al. ( eds . ), The Encyclopedia of Molecular disclosure in light of the detailed description . All such Biology , published by Blackwell Science Ltd . , 1994 ( ISBN modifications are intended to be included within the scope of 0 -632 -02182 - 9 ) ; Benjamin Lewin , Genes X , published by the appended claims. Jones & Bartlett Publishing , 2009 ( ISBN - 10 : 0763766321) ; Specific elements of any of the foregoing embodiments Kendrew et al. ( eds. ), Molecular Biology and Biotechnol- 20 can be combined or substituted for elements in other ogy : a Comprehensive Desk Reference , published by VCH embodiments . Furthermore , while advantages associated Publishers , Inc. , 1995 (ISBN 1 -56081 - 569 - 8 ) and Current with certain embodiments of the disclosure have been Protocols in Protein Sciences 2009, Wiley Intersciences, described in the context of these embodiments , other Coligan et al. , eds . embodiments may also exhibit such advantages , and not all Unless otherwise stated , the present invention was per - 25 embodiments need necessarily exhibit such advantages to formed using standard procedures, as described , for example fall within the scope of the disclosure . in Sambrook et al. , Molecular Cloning: A Laboratory The technology described herein is further illustrated by Manual (4 ed . ), Cold Spring Harbor Laboratory Press , Cold the following examples which in no way should be con Spring Harbor, N . Y . , USA ( 2012 ) ; Davis et al. , Basic Meth - strued as being further limiting . ods in Molecular Biology , Elsevier Science Publishing, Inc ., 30 New York , USA (1995 ); or Methods in Enzymology : Guide EXAMPLES to Molecular Cloning Techniques Vol. 152 , S . L . Berger and A . R . Kimmel Eds. , Academic Press Inc. , San Diego , U . S . A . The data provided herein , e . g ., in the figures and else ( 1987 ) ; Current Protocols in Protein Science (CPPS ) ( John where, show that a microbial consortium of several species E . Coligan , et . al. , ed ., John Wiley and Sons, Inc. ) , Current 35 (i .e . , 2 , 3 , 4 , 5 , or 6 species, for example ) can protect against Protocols in Cell Biology (CPCB ) ( Juan S . Bonifacino et. al. developing food allergy in a mouse model. Treatment with ed . , John Wiley and Sons , Inc . ) , and Culture of Animal such a consortium of bacteria can reverse TH2 programming Cells : A Manual of Basic Technique by R . Ian Freshney, of Tregs . Treatment and /or prevention of food allergy using Publisher : Wiley - Liss ; 5th edition ( 2005 ) , Animal Cell Cul- a similar microbial consortium of microbes in humans is ture Methods (Methods in Cell Biology, Vol. 57, Jennie P. 40 specifically indicated . Mather and David Barnes editors , Academic Press, 1st Further methods for testing or measuring the efficacy of a edition , 1998 ) which are all incorporated by reference herein microbial consortium in a mouse model of food allergy are in their entireties . known in the art and / or can be found in e . g ., Noval Rivas et Other terms are defined herein within the description of al. J Allergy Clin Immunol ( 2013 ) 131 ( 1 ): 201 -212 or Noval the various aspects of the invention . 45 Rivas et al ., Immunity ( 2015 ) 42 : 512 - 523 , the contents of All patents and other publications, including literature which are each incorporated herein in their entirety . references , issued patents , published patent applications, and co -pending patent applications; cited throughout this appli Example 1 : Therapeutic Microbiota to Treat Food cation are expressly incorporated herein by reference for the Allergy purpose of describing and disclosing , for example , the 50 methodologies described in such publications that might be Summary used in connection with the technology described herein . Food allergy is a growing national problem , affecting 6 % These publications are provided solely for their disclosure of children , and 3 % of U . S . teens and adults . Unfortunately prior to the filing date of the present application . Nothing in for these children and their families, the standard of care this regard should be construed as an admission that the 55 remains to avoid offending foods and manage symptoms as inventors are not entitled to antedate such disclosure by they occur. Therapies using oral desensitization , alone or virtue of prior invention or for any other reason . All state with anti -IgE (OmalizumabTM ) , remain experimental with ments as to the date or representation as to the contents of limited success . Needed are therapies that target the aberrant these documents is based on the information available to the immune responses. As such , this study shows the use of gut applicants and does not constitute any admission as to the 60 microbiota as a therapeutic intervention to promote toleriz correctness of the dates or contents of these documents . ing responses that can prevent or mitigate effects of Th2 / The description of embodiments of the disclosure is not allergic responses . intended to be exhaustive or to limit the disclosure to the Food allergies occur with development of Th2 - allergic precise form disclosed . While specific embodiments of, and responses to foodstuffs , in contrast to tolerizing T - regulatory examples for, the disclosure are described herein for illus - 65 responses that mitigate such responses mucosally . The Th2 trative purposes , various equivalent modifications are pos - responses promote food antigen - specific IgE antibody and sible within the scope of the disclosure, as those skilled in recruitment ofmucosal mast cells , in contrast to regulatory US 10 , 265 , 349 B2 59 60 responses, which inhibit these effects . Once sensitized to one with approximately equal biomass of each component or more food antigens, re - exposure can induce life - threat - organism to a final concentration ~ 5 .0x108 colony forming ening anaphylactic responses. Capacity to promote tolerizve units (CFU ) /mL . Input culture volumes for each species ing responses supports a broad -based therapeutic approach have been in the range of 100 mL - 1L . As needed , cultures that can act at the earliest stages of exposure as well as in the 5 with a stationary phase biomass < 5x108 CFU /mL are con already - sensitized patient to prevent aberrant allergic centrated by centrifugation with re - suspension handled responses across a spectrum of foodstuffs . Leveraging the genetically susceptible IL4RA F709 under anaerobic conditions . mouse model [ 1 , 2 ] of food allergy defined human commen When mixed , the total biomass remains approximately sal communities that can both prevent and cure food aller - 10 5x108 CFU /mL . 2 mL aliquots are placed in cryovials with gies in preclinical models have been developed . These an anaerobic / pre- reduced atmosphere , snap frozen on liquid communities leverage a new therapeutic pathway for nitrogen and stored at - 80° C . until use . Rapid freezing has patients — immunomodulation from the luminal side of the shown to have < 1 / 2 log effects on the biomass of the gut, the space in which the gut microbiota resides. Human component organisms and no effect on efficacy in animal gut microbiota consists of many hundreds of species that 15 models . For studies , tubes are thawed and mice administered provide critical functions in normal human development and 200 uL of this solution weekly to twice weekly by oral health , from maturing of the immune system , providing gavage , resulting in a total introduced biomass of 1x108 essential nutrients such as B vitamins and vitamin K , and CFU /mouse . The measurements of gut contents in adult assisting in digestion and metabolism of dietary and exog mice ( stomach through anus ) range from 4 - 8 mL ofmaterial . enous compounds , including drugs and ingested foodstuffs . 20 The gavaged consortium is thus 2 . 5 - 5 % of the total volume Background of contents in the mouse gut and > 10 % of the volume of The therapeutic consortia consist of defined and cultur - contents in the small bowel. able human commensal strains that stimulate protective In terms of pre - existing microbial biomass from the regulatory T cell responses in the gut. Two protective conventional microbiota — the mouse small intestine on communities have been developed , Gut - Protect I (GP - I ) and 25 average has ~ 104 CFU /mL in proximal duodenum with Gut- Protect II (GP - II ) . All have complete or contig -level increase to 108 CFU /mL in the ileum . Biomass increases to genomic sequences, and select members from each group 10° - 1010 CFU /mL in the cecum and colon . From the stand can be genetically manipulated . In addition , a third commu point of microbial biomass at locations in the mouse small nity has been developed that demonstrates worsened effects (Negative Control Consortium , Neg -CC ) , which is provid - 30 bowel, the primary site of action of the consortia to promote ing further information on dysbiotic effects in vivo and regulatory T cell responses, the consortium is 10 ,000x the potential biomarkers to assist in diagnosis and selection of biomass of the duodenal microbiota , and 1 - 2x the biomass therapy . of the jejunal and ileal microbiota . (1 ) Gut- protect I : Community of culturable gut commen In comparison , the adult human gut may contain 4 . 5 L of sals that has demonstrated treat- to -protect and treat- to -cure as35 material, of which 1 L relates to ingested foodstuffs with 3 . 5 efficacy in food antigen sensitization of IL4RA F709 mice . L of secretions including saliva , bile , and other fluids from ( 2 ) Gut -protect II : Community of culturable gut commen the pancreas and intestines [ 3 ] . These fluids and electrolytes sals that has demonstrated robust treat - to -prevent efficacy in are largely resorbed in the right colon , subsequent to recal animal models and less robust treat - to - cure efficacy than compaction and passage . Within the intestines, the biomass Gut -protect I . However, in standard solutions administered 40 of organisms also varies, with the highest concentration in to the host, this community tolerates greater ambient air the cecum and right side of the colon ( 1010 - 1012 CFU /mL ) . exposure than the Gut- protect I community . In contrast, in the small intestine the believed site of ( 3 ) Negative Control Community : Community of cultur- action , the biomass also ranges from 104 CFU /mL in the able gut commensals that promote food antigen sensitization duodenum to 108 CFU /mL in the ileum [ 4 , 5 ] . in treat- to -prevent and treat - to - cure regimens . This commu - 45 Human Dosing nity is defining the nature of dysbiosis in food allergy and The CFU / dose for humans is based on the following supporting development of biomarkers that could predict parameters : microbiota - derived factors that enhance susceptibility to ( 1 ) Treatment of C . difficile with oral capsule formulations development of food allergies . of human stool: Data from OpenBiome and other groups In pre -clinical models of food allergy to egg , leveraging 50 have shown successful treatment of C . difficile colitis with a susceptible mouse model that does not require the use of adjuvants , GP- I and GP - II each demonstrated treat- to - pre capsule formulation that administers 3 - 5x10º CFU in a vent efficacy , when used in a period of sensitization to the range of 12 - 30 capsules taken per one - time dose [ 6 ] . A allergy - inducing foodstuff . GP - I was also effective in treat standard 12 -capsule regimen is expected to deliver approxi to - cure regimens when used in animals that had already been 55 mately" 4 .2x10° CFU per dose . sensitized to egg protein , to the point that re -exposure would ( 2 ) Alter the small intestinal microbiota to promote immu induce life - threatening anaphylactic responses. In contrast, nomodulation . An encapsulated formulation releasing con the negative control community worsened effects , and pro tents in the proximal small bowel will deliver a dose of vides further insights as to the underlying dysbiosis that may 3 -5x10° CFU , exceeding the duodenal biomass by a factor contribute to development of food allergies , while also 60 of 10 ,000 , and approaching a 1 : 1 ratio with communities in providing potential biomarkers to identify individuals at the jejunum and ileum . risk , or for whom microbial therapy may be efficacious. Other formulations including nanoparticles in liquid , with Consortia Development optional pre -biotic compounds to enhance colonization and For pre - clinical studies in mice the component members viability , or a reconstituted lyophilisate are contemplated , are grown individually in nutrient- rich media under appro - 65 however given the need to prevent exposure to oxygen and priate anaerobic conditions , quantitated for biomass, and for ease of storage and administration , the first formulation then the consortium is mixed under anaerobic conditions uses encapsulated material. US 10 , 265 , 349 B2 61 62 Administration the inoculum enhance viability in capsules and once released Given the obligately anaerobic nature of the component in vivo . Materials can include preservatives and prebiotic species, phase I studies will use encapsulated formulations compounds. with the following properties: Stage II : It is further contemplated herein that the con Stage I : 5 sortia described herein are formulated as a liquid formula Can be swallowed by an adult or child > 8 years of age . tion that can be administered to infants and young children . Excludes oxygen It is contemplated herein that such formulations comprise Holds a volume so that a person needs to take 15 or less mixtures of spores from sporulating species , leveraging capsules per dose non - sporulating obligate anaerobes with limited aerotoler Can be stored frozen ( - 20° C . or - 80° C . ) and thawed 10 ance, and including reducing factors in a liquid formula to buffer against short - term exposure to oxygen in ambient air prior to administration and upon entry into the digestive tract. Compounds such as Releases contents after passage through the stomach the amino acid cysteine or n - acetylcysteine, which have In one embodiment, the capsules used by OpenBiomeTM been used therapeutically in infants and have a robust safety for oral FMT therapy are used to encapsulate the GP - I and 15 profile are contemplated [ 7 , 8 ] . GP - II mixtures [ i ] . Other options are also available com Additional pre - clinical animal models for use in testing mercially and contemplated herein . In some embodiments , formulations include e. g ., neonatal swine models of food the capsules consist of frozen material ( in order to ensure an allergy, including ones for foodstuffs common in the diet of adequate productuct ) that is thawed prior to administration and both humans and pigs 19 ) . is encapsulated , free of oxygen , with material that survives 20 intact into the small intestine . REFERENCES Scale of Culture The animal studies used pilot cultures in the range of 1 . Mathias C B , Hobson SA , Garcia -Lloret M , Lawson G , 100 - 1000 mL . To generate human doses , the culture is Poddighe D , Freyschmidt E J, Xing W , Gurish M F , Chatila scaled by at least a factor of 10. The following steps are 25 TA , Oettgen H C . IgE -mediated systemic anaphylaxis and contemplated herein . impaired tolerance to food antigens in mice with enhanced ( 1 ) Perform growth curves in different media condi- IL - 4 receptor signaling . J Allergy Clin Immunol. 2011 tions — to optimize growth conditions and correlate an March ; 127 ( 3 ) : 795 - 805 . el - 6 . OD600 with plated biomass . 2 . Noval Rivas M , Burton O T , Wise P , Zhang Y Q , ( 2 ) Grow the component members anaerobically in liquid 30 Hobson S A , Garcia Lloret M , Chehoud C , Kuczynski J . DeSantis T , Warrington J, Hyde E R , Petrosino JF , Gerber media . Media is pre - reduced and incubated at 37° C . G K , Bry L , Oettgen H C , Mazmanian S K , Chatila T A . A with some level of agitation ( e . g . , 150 rpm or with microbiota signature associated with experimental food stirring/ fermenter baffles ) to insure a maximal culture allergy promotes allergic sensitization and anaphylaxis . J density . Depending upon the fermenter system , nitro - 35z Allergy Clin Immunol. 2013 January ; 131( 1 ) : 201 - 12 . gen or anaerobic gas mixtures can be sparged to main 3 . Secretions in the GI tract- available on the world wide tain anaerobic conditions. However, none of the com web at: en .wikibooks . org /wiki /Medical _ Physiology /Gastro ponent species require Hy or CO2 for growth , beyond intestinal_ Physiology / Secretions maintaining appropriate acid / base balance . 4 . Genes Nutr. 2011 August ; 6 ( 3 ) : 209 -240 ( 3 ) Concentrate select members as needed to obtain 40 5 . Stool substitute transplant therapy for the eradication of desired input density : commonly done by centrifuga Clostridium difficile infection : ‘RePOOPulating the gut. tion at 5 - 10 K RPM with pull - off of supernatant under Microbiome Journal Open Access ( 2013 ) DOI: 10 . 1186 / anaerobic conditions and resuspension in a lesser vol 2049- 2618 - 1- 3 . ume of new culture media or appropriate suspension 6 . Open Biome FMTcapsules F30 and G3: available on buffer. The new culture density is confirmed by OD600 45 the world wide web at openbiome. org / fmtcapsules/ reading and viability by plating to solid media . 7 . Zlotkin , S H , et al . Cysteine supplementation to cys ( 4 ) Aggregate the cultured into the combined consortium : teine- free intravenous feeding regimens in newborn infants . Estimated biomass from the OD600 readings are used Am J Clin Nutr. 1981 , 34 ( 5 ) : 914 - 923 . to estimate the volume and prepare the aggregate . 8 . Marzullo , L . An update of N - acetylcysteine treatment ( 5 ) Prepare capsules : done under anaerobic conditions to 50 for acute acetaminophen toxicity in children . Curr Op Peds . preserve viability . 2005 , 17 (2 ): 239 - 245 . ( 6 ) Store capsules : optimal to store at conditions available 9 . Helm , R H et al. A neonatal swine model for peanut clinically , e . g . - 20° C . allergy . JACI. 2002 , 109 ( 1 ) : 136 - 142 . ( 7 ) Quality Control: In addition to QC for prior steps and media , the final community will be evaluated to insure 55 Example 2 : OTU Clustering Method for Data From the appropriate species are present and in desired viable Human and Animal Studies biomass . Analyses on materials for pre - clinical studies used 16S rRNA gene phylotyping with culture a qPCR DNA extraction and sequencing for 16S rRNA gene based methods. Metagenomic approaches may also be phylotyping . A multiplexed amplicon library covering the used to rule - out contamination with nonbacterial spe - 60 V4 region of the 16S rDNA gene was generated from DNA cies or viruses . extracted from human stool, mouse fecal pellets or segments It is further contemplated herein that growth conditions of snap - frozen gut tissues using MO BIOTM Power - FecalTM are optimized for the scaled cultures . DNA Isolation Kits (MO BIOTM Laboratories) with custom In some embodiments, media formulations are developed modification to enhance lysis of Gram positive commensals such that they lack animal products and / or substrates that 65 with thick cell walls . The rest of library preparation followed might be associated with sensitizing antigens in foodstuffs . the protocol of [ 1 ] with dual - index barcodes . Aggregated In addition , one of skill in the art can assess if additives to libraries are sequenced with paired - end 250 bp reads on the US 10 , 265 , 349 B2 63 64 IlluminaTM MiSeq platform . The aggregate library pool was pplacer software package to perform phylogenetic place size selected from 300 - 500 bp on a PippinTM prep 1. 5 % ment of individual OTU [ 4 ]. Pplacer uses a likelihood -based agarose cassette (Sage SciencesTM ) according to the manu methodology to place short sequencing reads of 16S rRNA facturer' s instructions. Concentration of the pool is mea amplicons on a reference tree , and also generates taxonomic sured by qPCR (Kapa BiosystemsTM ) and loaded onto the 5 classifications of the short sequencing reads using a least common ancestor -based algorithm . The reference tree MiSegTM ( IlluminaTM ) at 6 - 9 PM with 20 % phiX spike - in to required for phylogenetic placement is generated using compensate for low base diversity according to IlluminaTM ' s full- length or near full -length > 1 ,200 nt) 16S rDNA standard loading protocol. sequences of type strains from the Ribosomal Database 16S rRNA Data preprocessing. Sequencing aims to obtain 10 Project (RDP ) [ 5 ] . 10 - 50K usable reads per sample after quality filtering . Raw For all statistical testing for 16S rDNA data analysis , sequencing reads were processed using the mothur software p -values were adjusted for multiple hypothesis testing using package ( v . 1. 35 . 1) [ 2 ] and custom Python and R scripts [ 3 ], the method of Benjamini and Hochberg (BH ) [6 ]. Heatmap which perform de -noising , quality filtering , alignment plotsin are generated using custom R scripts [ 3 ] . against the ARB Silva reference database of 16S rDNA gene 15 Alpha diversity values ( richness of a sample in terms of sequences, and clustering into Operational Taxonomic Units the diversity of the OTUs observed in it) were calculated (OTUS ) at 97 % identity . using Shannon entropy to measure diversity in each sample . 16S rRNA Data Analysis . To statistically test for differ Beta -diversity values (distance between samples based on ences between control and food allergic subjects in abun - differences in OTUs present in each sample ) were calculated dances of microbial taxa (OTUS ) , the DESeq2 software using the unweighted /weighted Unifrac dissimilarity mea package was employed to support of analyses relative to sure , to assess differences in overall microbial community host co - variates such as age , food allergy status , diet and structure . antibiotic use in human cohort, OTUs showing significant ( 3 ) OTU Mappings of the Defined Species differences were defined by : ( 1 ) adjusted p - value < = 0 . 1 ; ( 2 ) The following operational taxonomic units map to the relative abundance > = 0 .01 in either control or food allergic o defined species , as identified in gnotobiotic mice colonized groups; ( 3 ) absolute value of log 2 fold changes > = 2 . with these consortia . Fecal pellets were subjected to the To improve the resolution of taxonomic calls and show above described 16S rRNA gene phylotyping over the V4 phylogenetic relationships, a separate method used the variable region . TABLE 2 Mapping of the defined therapeutic species to OTU based on the 16S rRNA V4 region . Species OTU taxonomic mappings , V4 region - Bacteroides Bacteria :Bacteroidetes : Bacteroidia :Bacteroidales fragilis Bacteria : Bacteroidetes : Bacteroidia : Bacteroidales :Bacteroidaceae Bacteria: Bacteroidetes :Bacteroidia :Bacteroidales : Bacteroidaceae: Bacteroides Bacteroides Bacteria : Bacteroidetes :Bacteroidia : Bacteroidales thetaiotaomicron Bacteria :Bacteroidetes : Bacteroidia : Bacteroidales: Bacteroidaceae Bacteria :Bacteroidetes : Bacteroidia :Bacteroidales : Bacteroidaceae :Bacteroides Bacteroides Bacteria : Bacteroidetes : Bacteroidia : Bacteroidales ovatus Bacteria : Bacteroidetes : Bacteroidia : Bacteroidales :Bacteroidaceae Bacteria :Bacteroidetes :Bacteroidia :Bacteroidales : Bacteroidaceae : Bacteroides Clostridium Bacteria :Firmicutes : Clostridia :Clostridiales : Peptostreptococcaceae bifermentans Bacteria : Firmicutes : Clostridia : Clostridiales : Peptostreptococcaceae :Clostridium cluster XI Clostridium Bacteria :Firmicutes :Clostridia : Clostridiales :Peptostreptococcaceae hiranonsis Bacteria : Firmicutes: Clostridia :Clostridiales : Peptostreptococcaceae : Clostridium cluster XI Clostridium Bacteria : Firmicutes :Clostridia : Clostridiales : Ruminococcaceae leptum Bacteria :Firmicutes :Clostridia : Clostridiales :Ruminococcaceae :Clostridium cluster IV Clostridium Bacteria :Firmicutes : Erysipelotrichia :Erysipelotrichales : Erysipelotrichaceae ramosum Erysipelotrichales :Erysipelotrichaceae : Clostridium cluster XVIII Clostridium Bacteria : Firmicutes :Clostridia : Clostridiales : sardiniensis Bacteria : Firmicutes: Clostridia : Clostridiales: Clostridiaceae 1 ( absonum ) Clostridium Bacteria :Firmicutes : Clostridia : Clostridiales :Lachnospiraceae scindens Bacteria : Firmicutes: Clostridia :Clostridiales : Lachnospiraceae : Clostridium cluster XIVa Parabacteroides Bacteria : Bacteroidetes: Bacteroidia : Bacteroidales :Porphyoromondaceae goldsteinii Bacteria :Bacteroidetes : Bacteroidia :Bacteroidales : Porphyoromondaceae :Parabacteroides Prevotella Bacteria: Bacteroidetes :Bacteroidia :Bacteroidales : tannerae Bacteria :Bacteroidetes :Bacteroidia :Bacteroidales :Prevotellaceae Bacteria :Bacteroidetes : Bacteroidia :Bacteroidales : Prevotellaceae : Prevotella US 10 , 265 , 349 B2 65 TABLE 3 Mapping of the dysbiotic consortium species to OTU based on the 16S rRNA V4 region Species OTU mapping Bilophila Bacteria :Proteobacteria : Deltaproteobacteria : Desulfovibrionales wadsworthia Bacteria : Proteobacteria :Deltaproteobacteria : Desulfovibrionales :Desolfovibrionaceae Bacteria :Proteobacteria : Deltaproteobacteria : Desulfovibrionales: Desolfovibrionaceae :Bilophila Enterobacter Bacteria : Proteobacteria :Gammaproteobacteria :Enterobacteriales cloacae Bacteria : Proteobacteria :Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae Bacteria : Proteobacteria :Gammaproteobacteria :Enterobacteriales :Enterobacteriaceae : Enterbacter Escherichia Bacteria :Proteobacteria :Gammaproteobacteria : Enterobacteriales coli Bacteria : Proteobacteria :Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae Bacteria : Proteobacteria :Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae :Escherichia Klebsiella Bacteria :Proteobacteria :Gammaproteobacteria :Enterobacteriales pneumonia Bacteria : Proteobacteria : Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae Bacteria : Proteobacteria :Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae :Klebsiella Proteus Bacteria :Proteobacteria :Gammaproteobacteria : Enterobacteriales mirabilis Bacteria :Proteobacteria :Gammaproteobacteria : Enterobacteriales :Enterobacteriaceae Bacteria :Proteobacteria :Gammaproteobacteria : Enterobacteriales : Enterobacteriaceae : Proteus

TABLE 4 Additional “ beneficial” OTU identified in the longitudinal pediatric human cohort as associated with protection from development of food allergy . Nearest species mapping (s ) with OTU taxonomic mappings with sequencing of the V4 region - pplacer Bacteria : Firmicutes :Clostridia : Clostridiales :Lachnospiraceae Clostridium hathewayi Bacteria :Firmicutes : Clostridia : Clostridiales :Lachnospiraceae : Clostridium cluster XIVa Bacteria :Firmicutes :Clostridia : Clostridiales :Lachnospiraceae : Hungatella Bacteria :Firmicutes :Clostridia : Clostridiales : Lachnospiraceae Clostridium nexile , Bacteria: Firmicutes : Clostridia: Clostridiales :Lachnospiraceae : Clostridium cluster Clostridium XIVa hylemonae, Clostridium glycyrrhizinilyticum , Clostridium scindens, Clostridium lavalense , Clostridium fimetarium , Clostridium symbiosum Bacteria : Firmicutes: Clostridia : Clostridiales :Ruminococcaceae Clostridium Bacteria : Firmicutes : Clostridia : Clostridiales :Ruminococcaceae :Clostridium cluster sporosphaeroides IV Bacteria :Firmicutes :Negativicutes :Selenomonadales : Veillonellaceae Dialister Bacteria : Firmicutes :Negativicutes : Selenomonadales :Veillonellaceae : Dialister proprionicifaciens, Dialister succinatiphilus Bacteria :Bacteroidetes :Bacteroidia :Bacteroidales : Porphyoromondaceae Parabacteroides Bacteria :Bacteroidetes : Bacteroidia :Bacteroidales :Porphyoromondaceae :Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides merdae Bacteria : Firmicutes: Clostridia : Clostridiales :Peptostreptococcaceae Peptostreptococcus Bacteria :Firmicutes : Clostridia : Clostridiales :Peptostreptococcaceae : Peptostreptococcus anaerobius Bacteria : Firmicutes : Clostridia : Clostridiales :Ruminococcaceae Subdoligranulum Bacteria : Firmicutes: Clostridia :Clostridiales : Ruminococcaceae : Subdoligranulum variabile Bacteria :Firmicutes :Negativicutes : Selenomonadales :Veillonellaceae Veilonella ratti Bacteria :Firmicutes :Negativicutes : Selenomonadales :Veillonellaceae : Veillonella US 10 , 265, 349 B2 67 68 TABLE 5 Additional “ dysbiotic” OTU identified in the longitudinal pediatric human cohort as associated with development of food allergy . Nearest species mapping with OTU taxonomic mappings with sequencing of the V4 region pplacer Bacteroidetes: Bacteroidia :Bacteroidales : Rikenellaceae : Alistipes Bacteroidetes: Bacteroidia :Bacteroidales : Rikenellaceae : Alistipes onderdonkii Firmicutes: Clostridia : Clostridiales :Lachnospiraceae Blautia Firmicutes :Clostridia : Clostridiales : Lachnospiraceae :Blautia wexlerae , Blautia henselae Bacteria :Proteobacteria :Deltaproteobacteria :Desulfovibrionales Bilophila Bacteria :Proteobacteria :Deltaproteobacteria :Desulfovibrionales : Desolfovibrionaceae wadsworthia , Bacteria :Proteobacteria :Deltaproteobacteria :Desulfovibrionales :Desolfovibrionaceae : Bilophila Desulfovibrio Bacteria :Proteobacteria :Deltaproteobacteria :Desulfbvibrionales : Desolfbvibrionaceae :Bilophila :Desulfovibrio species Firmicutes: Bacilli :Lactobacillales : Lactobacillaceae :Lactobacillus Lactobacillus johnsoni Bacteria :Proteobacteria :Betaproteobacteria : Burkholderales : Parasutterella Bacteria :Proteobacteria :Betaproteobacteria : Burkholderales: Sutterellaceae excrementihominis Bacteria :Proteobacteria : Betaproteobacteria : Burkholderales: Sutterellaceae : Parasutterella Firmicutes :Clostridia : Clostridiales : Lachnospiraceae Roseburia Firmicutes :Clostridia : Clostridiales : Lachnospiraceae :Roseburia inulinivorans

REFERENCES published data have shown that bacterial cell wall fractions 2 from members of the negative control consortium can pro 1 . Kozich , J . J ., et al. , Development of a dual- index sequenc mote aberrant stimulation of both allergic ( Th2 ) and pro ing strategy and curation pipeline for analyzing amplicon inflammatory ( Th1) responses. The distinct portions of these sequence data on the MiSeq Illumina sequencing plat - molecules that skew towards tolerance vs. allergy or inflam form . Applied and environmental microbiology, 2013 . 30 . mation highlight the interplay between mammalian hosts 79 ( 17 ): p . 5112 -5120 . and colonizing microbiota , including the microbial products 2 . Schloss, P . D ., et al. , Introducing mothur : open - source , that signal the host to maintain a healthy homeostasis versus platform - independent, community - supported software for elicit pathogenic immune responses. describing and comparing microbial communities . Appl Mucosal and immunoprotective functions of microbial Environ Microbiol, 2009. 75 ( 23 ) : p . 7537 -41 . 35 end -products of metabolism : Short chain fatty acids (SCFA ) 3 . McMurdie , P. and S . Holmes, phyloseq : An R package for are natural end -products of microbial anaerobic fermenta reproducible interactive analysis and graphics of micro - tion as are additional small molecule metabolites from biome census data . PloS ONE , 2013 . 8 ( 4 ) : p . e61217 . anaerobic fermentation of different carbon sources . End 4 . Matsen , F ., R . B . Kodner, and E . V . Armbrust, pplacer : products such as butyrate have been shown to provide a linear time maximum - likelihood and Bayesian phyloge - 40 primary energy source to the gut epithelium and to contrib netic placement of sequences onto a fixed reference tree . ute to the development of tolerizing responses in mucosal BMC bioinformatics, 2010 . 11 ( 1 ): p . 538 . locations . The consortia selected produce a dominance of 5 . Cole , J. R ., et al ., Ribosomal Database Project: data and butyrate and propionate from the fermentation of simple and tools for high throughput rRNA analysis. Nucleic acids complex carbohydrates that may be in the gut lumen , per the research , 2014 . 42 ( D1) : p . 1633 -42 . 45 diet and secretion of host factors . These factors would likely 6 . Benjamini, Y . and Y . Hochberg, Controlling the false act in combination with other microbial activities to mediate discovery rate : a practical and powerful approach to the desired immunomodulatory effects . multiple testing . Journal of the Royal Statistical Society Biochemical activities: The species selected perform the Series B , 1995 . 57 ( 1) : p . 289 -300 . full complement of bile acid transformations and also trans 50 form a variety of other molecules including other choles Example 3 : Microbiology -Level Activities Used in terol- derivatives , biogenic amines, lipids and production of Selection of Defined Species aryl hydrocarbons which may serve as microbial sidero phores, quorum sensing molecules and other metabolic The species in the defined consortia were selected per intermediates within the microbial cell. Such metabolites are known biochemical, immunologic and microbiologic func - 55 potentially capable of stimulating host aryl- hydrocarbon tions with capacity to affect beneficial immunomodulatory receptor ( AHR ) pathways which have also been demon responses in the host. Without wishing to be bound by strated to promote tolerizing responses in the gut mucosa . theory , microbiologic mechanisms of action can include the Gut conditioning: Microbiologically , select members of following. the consortia are known to aid the subsequent colonization , Adjuvant effects of microbial products to stimulate the 60 biochemical and further immunoprotective roles of other development of regulatory T cells through TLR > MyD88 species. Both Bacteroides fragilis and Bacteroides thetaio and other immune cell pathways . The production of key taomicron, when included in defined flora , assist the growth microbial antigens from commensal anaerobes, including of more fastidious members of the Bacteroidetes, Firmicutes their lipoteichoic acid ( LTA ) , exo - polysaccharides ( PSA ), and Actinobacteria . Clostridium ramosum has demonstrated LPS , bacterial flagellin , and bacterial DNA can act through 65 comparable effects in defined colonizations of germ - free stimulating toll - like - receptor pathways to skew mucosal T mice with other commensals . Effects are multi - factorial, and cells to a regulatory vs. allergic phenotype . In contrast, include maturing of gut epithelial responses , altered host US 10 ,265 , 349 B2 69 70 secretion of glycoconjugates which can serve as carbon protective against the development of food allergy could be sources for the commensal flora , enhancing gut peristalsis cured of allergic sensitivity , conventional ( i . e ., non - germ and digestion , reducing lumen gut oxygen tension so more free ) IL4RA F709 mice were sensitized to ovalbumin by 8 obligately anaerobic species can flourish , and releasing weekly treatments with OVA -SEB as performed in the metabolites, and /or extracellular products of microbial 5 experiments described above (see FIG . 23A for the experi digestion which support the growth of additional species by providing carbon and/ or nitrogen sources, vitamins, and mental timeline ) . The animals were then treated with anti other essential micronutrients . biotics to knock out their natural gut bacteria , before being Reducing the biomass of dysbiotic or pathogenic species : treated with the GP - I , GP - II or NCC consortia using four Animal models conducted by our group have also shown . weekly doses . After the fourth weekly dose of the test that the species in the gut protect communities can reduce 10 consortia , the animals were challenged with OVA . The data , the biomass of the Proteobacterial species in the negative which examined the same criteria examined in Examples 4 control consortium . Without wishing to be bound by theory, and 5 , show that animals treated with the GP -I (Clostridi mechanistically these biomass reductions also reduce the ales ) and GP - II (Bacteroidetes ) consortia were substantially antigen burden of products from these species that prefer protected against allergic reaction , while those receiving the entially skew towards allergic responses . 15 negative control (Proteobacteria ) consortium were not (see FIG . 23B - H ) . These data demonstrate that not only can food Example 4 : GP - I and GP - II Consortia are Effective allergy be prevented from developing through administra in Treat- To - Prevent Food Allergy in Conventional tion of the microbial consortia described herein , but estab Wild - Type and IL4RA F709 Mice lished food allergy can also be treated by administration of 20 the same protective consortia . The protective effects of consortia GP - I ( Clostridial spe cies) and GP - II (Bacteroidetes species ) were examined in Example 7 : GP - II Consortium ( Bacteroidetes ) conventional and food allergy -prone IL4RA F709 mice. In Protects Against Food Allergy Without Prior this series of experiments, the animals were conventional, Antibiotic Knockdown of the Flora i. e . , not germ - free . Animals were treated with a course of 25 oral broad - spectrum antibiotics one week prior to initiating To examine whether it is necessary to first knock down the sensitization with egg ovalbumin (OVA ) and staphylococcal natural gut microbiota via antibiotic treatment in order to enterotoxin B (SEB ). After antibiotic treatment, the micemice obtain protection in conventional mice, such animals were received weekly doses of the GP - 1, GP - II or negative control administered 8 weekly doses of GP - I and GP -II consortia or consortia (NCC ) , and weekly doses of OVA - SEB before 30 no additional bacterial treatment, while sensitizing mice to challenge at week 8 with oral ovalbumin . See FIG . 21A . OVA with weekly OVA - SEB treatments over the course of Following challenge , animals were examined for tempera 8 weeks (see FIG . 24A for the experimental timeline ) . ture drop (FIG . 21B ) , total and OVA - specific IgE titers (FIG . Subsequent challenge with OVA demonstrated that , in the 21C ) , mast cell protease - 1 levels (FIG . 21D ), mast cell absence of natural flora knockdown prior to treatment with recruitment to the small bowel ( FIG . 2E ) and the develop - 35 GP - 1 or GP - 11 , the Bacteroidetes consortium , GP - 11 , pro ment of FoxP3 + regulatory T cells ( FIGS . 21F and G ) versus vided protection against the development of food allergy IL - 4 producing T cells ( FIGS . 21H and I ). The data clearly (see FIG . 24B - L ) . It is specifically contemplated that the show that the Clostridiales and Bacteroidetes consortia administration of a combination of GP - II with one or more , (GP - I and GP- II , respectively ) protected against allergy as or even all of the species ofGP - I would provide an improved measured by these criteria , while animals treated with the 40 effect, in terms of initial response or protection and / or in negative control consortium (denoted “ Proteobacteria ” ) or terms of the persistence of such protection . no bacteria showed a clear allergic response . Thus, GP - 11 and GP - II are effective to prevent the development of food Example 8 : The GP - I Consortium (Clostridiales ) allergy. can Cure Food Allergy Without the Use of 45 Antibiotics in Conventional Mice Example 5 : GP - I and GP - II Consortia Protect To examine whether it is necessary to knock down the Germ -Free Mice in Treat- to -Prevent Regimens natural gut microbiota in order to cure food allergy in The protective effects of the GP - I and GP - II consortia conventional mice , conventional wild -type and IL4RA F709 were examined in germ - free mice treated with saline (PBS ) 50 mutant mice were sensitized to ovalbumin via 8 weekly or with OVA -SEB . The germ - free mice received either no doses of OVA - SEB , followed by twice -weekly administra bacteria or consortia GP - I or GP - II prior to 7 weekly tion of the GP - I (Clostridiales ) consortium for 4 weeks, sensitizing doses of OVA -SEB (see FIG . 22A ) . Challenged without prior antibiotic knockdown of the natural gut micro on the gth week with OVA , the mice were examined for biota ( see FIG . 25A for the experimental timeline ) . When evidence of allergic reaction as described in Example 4 . The 55 challenged after the four weeks of GP - l administration , the data (see FIGS. 22B - H ) clearly show that unlike animals data show that the GP - I consortium was effective to reduce receiving no bacteria . germ - free animals administered the allergic symptoms by all measures examined in both the GP - I and GP - II consortia experienced substantially no aller wild - type and allergy -prone animals (See FIG . 25B - I) . The gic reaction upon challenge with the sensitizing food aller data indicate that the administration of the GP - I consortium gen . 60 is able to cure food allergy in the presence of the natural gut flora — that is , it is not necessary to first knock down the Example 6 : GP - I and GP - II Consortia Cure Food natural gut microbiota to effectively treat food allergy using Allergy in Conventional IL4RA F709 Mice ; protective microbial consortia such as the GP - I consortium . Negative Control Consortium Does Not The invention claimed is : 65 1 . A pharmaceutical composition , comprising : To test whether animals that had been sensitized to food ( i ) a purified mixture of live bacteria for treatment of an allergen before treatment with consortia shown herein to be inflammatory disorder in an individual in need thereof, US 10 , 265 , 349 B2 71 72 wherein the purified mixture of live bacteria consists 11 . The pharmaceutical composition of claim 10 , wherein essentially of Clostridium bifermentans and the pharmaceutical composition is formulated for oral Clostridium hiranonis ; and administration . ( ii ) a pharmaceutically acceptable carrier , wherein the 12 . The pharmaceutical composition of claim 10 , wherein pharmaceutical composition is formulated for intestinal15 5 the live bacteria in the purified mixture further comprises Bacteroides fragilis, Bacteroides thetaiotaomicron , Bacte delivery. roides ovatus, Parabacteroides goldsteinii , or Prevotella 2 . The pharmaceutical composition of claim 1 , wherein tannerae . the pharmaceutical composition is in the oral dosage form of 13. The pharmaceutical composition of claim 10, wherein a capsule , a reconstituted lyophilisate , a food item , a liquid , inflammatory disorder is a food allergy . gel , or fluid - gel. 14 . The pharmaceutical composition of claim 1 , wherein 3 . The pharmaceutical composition of claim 1 , wherein the purified mixture of live bacteria comprises species the purified mixture of live bacteria further comprises at present in a total amount of at least 1x10 CFUs. least one species of Bacteroides. 15 . The pharmaceutical composition of claim 1, wherein 4 . The A pharmaceutical composition comprising: (i ) a the purified mixture of live bacteria comprises species purified mixture of live bacteria for treatment of an inflam - - present in a total amount of at least 1x10° CFUs . matory disorder in an individual in need thereof, wherein the 16 . The pharmaceutical composition of claim 6 , wherein purified mixture of live bacteria consists essentially of the purified mixture of live bacteria comprises species Clostridium bifermentans, Clostridium hiranonis , present in an amount of at least about 1x108 CFUs/ml . Clostridium ramosum , Clostridium scindens, Clostridium 20 17 . The pharmaceutical composition of claim 6 , wherein leptum , and Clostridium sardiniensis and 20 the purified mixture of live bacteria comprises species ( ii ) a pharmaceutically acceptable carrier , wherein the present in substantially equal biomass . pharmaceutical composition is formulated for intestinal 18 . The pharmaceutical composition of claim 6 , wherein delivery . the pharmaceutical composition is in the oral dosage form of 5 . The pharmaceutical composition of claim 1 , wherein 2 a capsule , a reconstituted lyophilisate , a food item , a liquid , the inflammatory disorder is a food allergy . 25 gel , or fluid - gel . 6 . The pharmaceutical composition of claim 1 , wherein 19 . The pharmaceutical composition of claim 6 , wherein the purified mixture of live bacteria comprises species the pharmaceutical composition is enteric coated . present in substantially equal biomass . 20 . The pharmaceutical composition of claim 6 , wherein 7 . The pharmaceutical composition of claim 1 , wherein 30 the inflammatory disorder is a food allergy . the purified mixture of live bacteria comprises species 30 21 . The pharmaceutical composition of claim 10 , wherein present in an amount of at least about 1x108 CFUs/ ml . the live bacteria in the purified mixture are : Clostridium 8 . The pharmaceutical composition of claim 1 , wherein ramosum , Clostridium scindens, Clostridium hiranonis , the purified mixture of live bacteria does not comprise any Clostridium bifermentans , Clostridium leptum , and of the species Escherichia coli, Klebsiella pneumoniae , 35 Clostridium sardiniensis . Proteus mirabilis , Enterobacter cloacae , Bilophila wads 35 22. The pharmaceutical composition of claim 10, wherein worthia , Alistipes onderdonkii , Desulfovibrio species, Lac the purified mixture of live bacteria comprises species tobacillus johnsonii , or Parasutterella excrementihominis. present in a total amount of at least about 1x10° CFUS. 9 . The pharmaceutical composition of claim 1 , wherein 23 . The pharmaceutical composition of claim 10 , wherein the purified mixture of live bacteria is present in an amount 10 the purified mixture of live bacteria comprises species sufficient to increase the proportion of T regulatory cells in present in a total amount of at least about 1x108 CFUS. a subject. 24 . The pharmaceutical composition of claim 10 , wherein 10 . A pharmaceutical composition comprising : the purified mixture of live bacteria comprises species ( i ) a purified mixture of live bacteria for treatment of anin presentpre in an amount of at least about 1x108 CFUs/ml . inflammatory disorder in an individual in need thereof, 45 25 . The pharmaceutical composition of claim 10, wherein wherein the live bacteria in the purified mixture con 45 the purified mixture of live bacteria comprises species sists of up to eleven bacterial species in total and present in substantially equal biomass . includes the following bacterial species : Clostridium 26 . The pharmaceutical composition of claim 10 , wherein ramosum , Clostridium scindens , Clostridium hirano the pharmaceutical composition is in the oral dosage form of nis , Clostridium bifermentans, Clostridium leptum , 50 a capsule , a reconstituted lyophilisate , a food item , a liquid , Clostridium sardiniensis ; and 30 gel , or fluid -gel . ( ii ). a pharmaceutically acceptable carrier , wherein the 27 . The pharmaceutical composition of claim 10, wherein pharmaceutical composition is formulated for intestinal the pharmaceutical composition is enteric coated . delivery.