1832 the treatment of IBSand callsfor carefully thatsuggests FMTmay benefi be ses before and aft and before ses trolled and trials fecal microbiome analy- comprise prospective, randomized con- ously validated. been Future studies should ofuse aquestionnaire that hadnot previ- rospective design,smallsample size, and eases. of participants the developed any dis- new were nolong-term sideeff was atransient increase infl (46%). Th was achieved innearly halfof our patients improvement of overall well-being, which term treatment goal inpatients with IBSis bloating (50%),and fl abdominal pain (67%), (72%),dyspepsia aft toms enced resolution or improvement of symp- months. between FMTand data collection was11 until FMTwas73months, and mean time Mean timefrom initial diagnosisof IBS predominant IBS,and one hadmixed IBS. dominant IBS,three hadconstipation- patients,these ninehaddiarrhea-pre- completed study the questionnaire. Of years; 54%female) were identifi FMT. and overall well-being before and aft of frequency bowelpepsia, movements, vals, abdominal pain, bloating, fl included length the of symptom-free inter- data were administered; study outcomes ing demographic and pre- and post-FMT patients. A41-item questionnaire solicit- by esophagogastroduodenoscopy inall fecal duodenum distal the or proximal jejunum A (5). suspension of 50–100 intoml wasinfused recommendations current ent and were screened inaccordance with therapeutic modalities. pressants, probiotics, antibiotics, or other tomatic relief changes, with dietary antide- IBS wasdefi on Rome IIICriteria and nonresponsive were identifi 2011and 2012 between October October tional treatment and underwent FMT who with were IBSwho not responsive to tradi- Letters to the Editor tothe Letters The Limitations of our study include its ret- In our study, 70%of patients the experi- A total of 13patients (mean age of 45 Donors were chosen by FMTrecipi- the American Journal American er FMT, specifi e only adverse event reported ned asfailure to achieve symp- ed. Diagnosisof IBSwasbased er FMT. Th of

GASTROENTEROLOGY atus (45%). Along- cly hs with those cally ects, and none and ects, ispilot study au; there atus; atus, dys- e and ed ca for cial er

Brandt LJ Aroniadis OC Mellow M M w o l l e M , C O s i d a i n o r A , J L t d n a r B . 4 Task Gastroenterology of College American 3. Brandt LJ Aroniadis OC f o w e i v r e v o n A . C O s i d a i n o r A , J L t d n a r B . 5 . Pre G Brostoff GC, Parkes 2. NewYork , BA A B , g n a T n u h C fi designed studies to support or refute our n leaie oii 1 FT a emerged has FMT (1). colitis ulcerative in of fecal microbiota transplantation (FMT) articlethe regarding therapeutic the value To theEditor: doi: 10.1 D h P , D M , i L g n o r u i Q Diarrhea inaPatient Resolves Sepsisand Transplantation With FecalMicrobiota the IntestinalMicrobiota and Reestablishmentof TherapeuticModulation 1 M Donowitz JE, Everhart RS, Sandler 1. REFERENCES Dr Brandt isaconsultant for CIPAC. CONFLICTOFINTEREST NewYork Montefi Bronx E-mail: , MD D M , i L u o h s e i J BA Zhao , Xiaofan Montefi Brandt, MD,MACG, BethIsraelMedicalCenter, NewYork City ndings. transplant for recurrent term follow-up of colonoscopic fecal microbiota 1):S1–35. 2009;104(Suppl Gastroenterol management of irritable bowel syndrome . Am J position statementevidence-based on the Force on Irritable Bowel Syndrome . An 2008;103:1557–67. Gastroenterol J roletheir inits pathogenesis and treatment . Am testinal microbiota inirritable bowel syndrome: 2013;78:240–9. Endosc Gastrointest outcomes . and indications, fecal microbiota transplantation: techniques, 2012;107:1079–87. Gastroenterol J Am infection . ntd tts Gsretrlg 2002;122:1500. Gastroenterology States . United Th eburden of digestive inthe selected diseases , ore MedicalCenter, NewYork City ore MedicalCenter New York 038/ajg.2014.299 lbrandt@montefi ore.org , , USA USA ; . 2

Correspondence: , 1 DivisionofGastroenterology, 1 We read with great interest

New York Qn e , MA He , Qin ,

1 Division ofGastroenterology, , MD D M , i L g n i N , , K n a l e h W , J 1 ang A M , g n Wa g n a y n e h C , , Cotiim diffi Clostridium

111 East210thStreet, 10467

1 LawrenceJ. , , et al. USA 1 d n a et al. et al. Gastroin- . , cile , Long- g n o L

1 , received FMTand report fi of patient asepsis with severe who diarrhea Here, cases. in these case the we describe possibility of microbiota-targeted therapy of raising sepsis, etiology the an interesting of gut microbiota isprobably relevant for tion of gut microbial community. Dysbiosis allows reconstitution of anormal composi- 4 ). It represents atherapeutic protocol that diffi Clostridium as an accepted treatment for recurrent 2900/mm Laboratory results showed white-cell count 23, andpressure blood the 79/55 mm Hg. was 39.3 respirations 118,the pulse °C, the colectomy. Onadmission, temperature the ously administered for 2years aft orcefradine ornidazole, were discontinu- anddiarrhea thus antibiotics, including She subsequently developed intermittent acolectomyunderwent inNovember 2010. with ulcerativewas diagnosed colitis and uncontrollable Th diarrhea. watery to our hospital of because fever high and a suspension of donor feces through a the imbalance Th and bacterium teriaceae especially opportunistic organisms inProteobacteria, and Bacteroidetes and by an overgrowth of of commensals the ciency inFirmicutes turbed, characterized by aprofound defi that microbiota the wasextensively dis- compositionrial of the patient. We showed techniques to characterize fecal the bacte- applied 16SrRNA gene-based molecular possibilitythe of intestinal dysbiosis, we faileddiarrhea to improve. Considering and supportive strategies, fever the and interventions with antibiotics, probiotics, Acinetobacterbaumannii were negative until 7days, yielded when nous antibiotics were given. cultures Blood and supportive intensive care plus intrave- patible with clinical signs of septic shock, was –6.7 mmol/l. Th bon dioxide of 23.8 mm Hg; excess base the sure of oxygen of 92.8 mm Hg, and of car- gas revealed apHof pres- 7.365,apartial 68,000/mm thromboplastin time44.5 s, and platelets thrombin time17.9 s, activated partial e fi A 29-year-old woman wasadmitted VOLUME 109 ndings ledto decision the to correct Alpha proteobacterium Alpha 3 lactate, blood 3.2 mmol/l, pro- Enterobacter cloacae 3 . Ananalysis of arterial blood | NOVEMBER 2014 cile via FMT. We administered -soitd irha (2– diarrhea -associated , , e fi Klebsiella pneumoniae Klebsiella ndings were com- nature publishinggroup . Despite 20-day ndings.

www.amjgastro.com ( , , Figure 1 Figure Enterobac- e patient e the er - ).

and Bacteroidetes, including ure 1a like microbial pattern following FMT( similarity (6.5%)shift patient’sthe microbiota low with avery to less than halfof pre-FMT. Signifi days, stool the volume ultimately declined tion. cultures Blood sterile. became At 21 and stool output the hadamarked reduc- ics. In nextday, the fever the went down, tube andnasoduodenal withdrew antibiot- Figure1 nature publishinggroup © 2014by theAmericanCollege ofGastroenterology 6, 7,9,and21days.CDindicatethesamplesfromhealthycontrols andthedonor. of allfragmentsinthesamelanegel.P0d,P1d,P3d,P4d,P6d, P7d, P9d,andP21drepresentthesamplescollectedfrom cal microbiotas.Leftpanel:thephylumlevel;rightspecieslevel. Therelativeintensityofeachbandisexpressed mean valuesofthesimilaritybetweenpatientanddonor (D1,D2,andD3).( similarities comparedwiththedonor. SimilarityindicesbetweensampleswererepresentedbytheDicecoeffi in therightpanel.Upperleft:clusteringdendrogrambasedonprofi with universalV3region-targetedprimers.Thenumbers1to28representthebandsforDNAsequencing,andbacterialspecie (DGGE). Rightpanel:representativefi ) Th ). . Molecularcharacterizationofthefecalbacterialmicrobiotas.(

Relative abundance (%) Similarity coefficient (%) 20 e bacterial species inFirmicutes species ebacterial 20 100 10 20 30 40 50 60 40 60 80 20 0 0 04 50 40 30 0 1 3 4 6 7 9 P21d P9d P7d P6d P4d P3d P1d P0d Bacteroidetes Others Proteobacteria Firmicutes

C1 32

C2 41

ed toward adonor- D1

D2 55 07 09 100 90 80 70 60 D3 Eubacterium Eubacterium 66 68 ngerprints of thefecalmicrobiotas.Theprofi les aregeneratedfromDGGEanalysesof16 S rRNA genefragments 72

P0d 72 cantly, aaatrie itsnsStreptococcuspneumoniae Parabacteroides distasonis Bacteroides capillosus Bacteroides coprocola Bacteroides fragilis Bacteroides salanitronis Bacteroides thetaiotaomicron Bacteroides vulgatus Lactococcus garvieae P1d 81 82 Fig-

P3d 88

P4d barrier, and aid treatment inthe of sepsis. dysbiosis, induce recovery of gut microbial reasoned that FMTcould counterbalance benefi microbiotas were associated with clinical specifi cantly depleted ( organisms inProteobacteria were signifi ably expanded, whereas opportunistic ensis spp (%) P6d D2 D3 D1 P9d P21d C1 C2 P6d P7d P4d P3d P1d P0d

. ., P7d , and Lactococcus garvieae ts ( c FMT-induced alterations ingut P9d eapar ldniEbceimrcaeEnterobactercloacae Weissella koreensis rectale Eubacterium Megasphaera elsdenii Paenibacillus mucilaginosus Enterococcus faecalis clariflavum Clostridium eligens Eubacterium 27 25 23 19 17 15 14 Figure 2 Figure

6 2 C1 P21d Bacteroides spp 20 26 28 13 14 16 10 C2 4

les. Thescale barindicatessimilarity(%).Lowerleft:shiftsofbacterialcommunity C1 26 25 24 22 19 18 17 11 14

a D1 4 3 1 9 7 6 Figure 1b Figure )Analysisofthefecalmicrobiotasbydenaturinggradientgelelectrophoresis basisof). Onthe data, we C2 23 21 15 17 P0d 6 20 D1 28 12 10

8 P1d Klebsiella pneumoniae Lactobacillus acidophilus saccharobutylicumClostridium sp.Clostridiales Enterobacter aerogenes Roseburia intestinalis

D2 28 16 13 21 15 20

, , P3d 2 remark- were ., ) Interestingly, ). Weissella kore- Weissella 11 17 14 D3 26 25 24 23 22 18 D2 9 6 5 4

15 12 24 P0d 10 P4d b 1 )Variations ofthepredominantbacterialcompositioninfe- 21 P1d 28 20 P6d 1 17 18 14 11 23 22 26 D3

P3d 9 8 7 6 4 3 - Others coli Escherichia bacterium Enterobacteriaceae Alpha proteobacterium Enterobacter ludwigii Pseudomonas fluorescens 15 21 20 19 27

25 P7d P4d 24

28 P9d

P6d 4 fi lishment of normal microbiota. Th ableFMT being to facilitate reestab- the approach, is,at which due inpart, least to patient benefi therapeuticota-based intervention. Th diagnosticindicatorsuseful for microbi- patient isdefi Th of treatingexperience with sepsis FMT. rst description of FMT asapotentially cient. Thedata presentedhereindicatethe edysbiosis of intestinal micobiota inthe The 19

In conclusion, we report our initial P21d 11 3 15 23 20 P7d 5 American Journal American P9d

P21d Band 27 21 20 19 18 17 16 15 14 13 12 11 28 26 25 24 23 22 10 9 8 7 6 5 4 3 2 1 ts from unconventional the asaproportion(%)ofthesum Enterobacter cloacae Enterobacter ludwigii difficile Clostridium Bacteroides coprocola Megasphaera elsdenii Bacteroides capillosus Enterobacter aerogenes bacterium Enterobacteriaceae coli Escherichia Shigella flexneri clariflavum Clostridium Klebsiella pneumoniae sp.Clostridiales Lactococcus garvieae Roseburia intestinalis Streptococcus pneumoniae rectale Eubacterium eligens Eubacterium Enterococcus faecalis Bacteroides thetaiotaomicron Alpha proteobacterium Pseudomonas fluorescens Bacteroides salanitronis Weissella koreensis Bacteroides vulgatus Bacteroides fragilis Parabacteroides distasonis Paenibacillus mucilaginosus speciesidentified Bacterial ned, providing potentially of the patientat0,1,3,4, s identifi

GASTROENTEROLOGY Letters to the Editor tothe Letters ed areshown is is the isthe e 1833

1834 Potential competing interests manuscript. decision to publish, or preparation of the in study design,data collection and analysis, (2012AA021007). Th R&D Program (863Program) of China (2013CB531403) and National High-tech Program (973Program) inChina ported by the National Research Basic Financial support have approved fi the and wrote manuscript. the Allof authors the Qiurong and Li Chenyang Wang analyzed data Ning contributed Li to interpretation of data. Xiaofan experiments. the Zhaoperformed Chenyang Wang, Chun Tang, QinHe, and Jieshou conceived Li and study. designedthe Specifi Guarantor of thearticle CONFLICTOFINTEREST patient treatment and fecal sampling. Yu, DrJianfeng Gong, and DrTao Gaoin We assistances the thank of DrWenkui ACKNOWLEDGMENTS clinical use. cedure and toward insepsis also broader validate effi the larger number of patients are required to patient may exist.Future studies with a of potentially pathogenic organisms to the negative to transmission risk, minimizethe tice. Although donor the stool istested cutting-edge technique into clinical prac- vides awonderful example of using the therapeutic alternative for and sepsis pro- Letters to the Editor tothe Letters The output ofstoolsinthepatient,whereasProteobacteriashowsaweakassociationwithit(red). bacterial taxasandstoolvolumeeachday. ThephylumFirmicutes(blue)andthespecies Figure2 Proteobacteria (red),andtheratioFirmicutes/Proteobacteria(orange)withdailypeaktemperatureofpatient.( American Journal American c author contribution . Correlativeanalysesbetweenspecifi c bacterialphylogroupsandclinicalfeatures.( and safetycacy of pro- the nal draft : Th : of e funders hadnorole efunders

isstudy wassup- GASTROENTEROLOGY : Qiurong MD, Li, PhD. Relative abundance (%) 20 40 60 80 0 submitted. 653. 753. 8539.0 38.5 38.0 37.5 37.0 36.5 : Qiurong and Li : None. : Firmicutes/Proteobacteria Firmicutes Proteobacteria Peak tem

p erature Brandt LJ Aroniadis OC Mellow M M w o l l e M , C O s i d a i n o r A , J L t d n a r B . 2 3. Brandt LJ . American Journal of Gastroenterology Gastroenterology of Journal American LJ . Brandt 3. doi: 10.1 FASGE AGAF, FACG, MD, Adler , G. Douglas With PancreaticCancer CT ScansinPatients Between theFirstTwo Status Changes EvaluationofTNM 1 A Makristathis W , Reinisch S, Angelberger 1. REFERENCES Nood EV , rieze A Nieuwdorp M M p r o d w u e i N , A e z e i Vr , V E d o o N . 4 Nanjing Surgery, NanjingUniversitySchoolofMedicine , MD D M , a m r a h S h s i h s A rse Cx , S RN MS, Cox, Kristen University SchoolofMedicine Research InstituteofGeneralSurgery, Nanjing MD, PhD,orJieshouLi, [email protected] Zhongshan Road JinlingHospital,ResearchInstituteofGeneral transplant for recurrent term follow-up of colonoscopic fecal microbiota 2013;108:1620–30. Gastroenterol J Am transplantation . microbiota among ulcerative colitis patients aft vary dynamics community bacterial Temporal C. diffi microbiota transplant (FMT)intreatment of Lecture: Intestinal microbiota and role the of fecal 2012;107:1079–87. Gastroenterol J Am infection . 177 – 85 . 177 –85. diffi infusion of donor feces for recurrent ( cile °C 038/ajg.2014.302 , 1 cile , MD D M , u h t o m a l l a N a h t e e G , ) China . N Engl J Med 2013 ; 368 : 407 – 15 . 2013;368:407–15. Med J Engl N .

infection . Am J Gastroenterol 2013 ; 108 : 2013;108: Gastroenterol J Am infection . . Correspondence: , Nanjing 0 1 2 3 4 1 or odd H. Baron D M , n o r a B . H d d To d n a 1 , MD D M , n u r b l i e H a t r a M , [email protected]

Clostridium diffi Clostridium Firmicutes/Proteobacteria 210002

Jinling Hospital, ,

No. 305East Relative abundance (%) 80 20 40 60

0 QiurongLi, , ...... 4.0 3.5 3.0 2.5 2.0 1.5 1.0 et al. China er fecal Clostridium Clostridium et al. 1 Lactococcus garvieae , Duodenal l a n e d o u D cile a

. E-mail: )CorrelationsoftherelativeproportionFirmicutes(blue), Long- g n o L Lactococus garvieae Proteobacteria Firmicutes

et al.

, upto to l2 h) (l/24 stool of Output

2 3 ,

( on CTscan second the disease metastatic ease on the fi A total of 22patients hadmetastatic dis- the follow-up scan inthe treatment group. wassignifi disease treatment CTscan ( ascomparedCT scan with 28by post- the malignant lymphadenopathy on fi the ment group hadfi was not changed: 27patients treat- inthe with 3.6 cm (0–10.7)( 0.28 cm: 3.9 cm (range 0.7–8.7)compared mean tumor sizesignifi tion group was42.8±42.6days ( averagethe observa- inthe timeinterval average was93.5±40.2days; timeinterval 68.5±48.3 days. In treatment the group, the val between CTscans inallpatients was group.observation Th remaining patients were assignedto the were assignedto treatment the group. Th initialtheir and follow-up CTscan and received oncologic treatment between (60F, 62M).Fift CT scan inpatients with pancreatic cancer. optimalmine the timeto obtain afollow-up (1–3). studied previously Th been has nosis atic cancer, although imaging before diag- following(CT) scan adiagnosisof pancre- the fi agreed upon timeframe for obtaining To theEditor: P eaim to of deter- study this wasto try For patients inthe treatment group, A total of 122patients were included value treatment inthe <0.0001).Overall, VOLUME 109 rst follow-up computed tomography (yellow)showstrongcorrelationwiththe b )Therelationshipbetweenspecifi c | NOVEMBER 2014 rst CTand 35patients had Th y percent of patients cantly more frequent on ndings consistent with ere isnouniversally eaverage timeinter- P P cantly decreased by =0.05). Nodal stage nature publishinggroup =.6. Metastatic =0.66).

www.amjgastro.com P <0.0001). rst rst e