US010413581B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 413 ,581 B2 Bafundo et al. (45 ) Date of Patent: Sep . 17 , 2019 (54 ) COMBINATION , COMPOSITION , AND (58 ) Field of Classification Search METHOD OF ADMINISTERING THE None COMBINATION OR COMPOSITION TO See application file for complete search history. ANIMALS (56 ) References Cited (71 ) Applicants : Phibro Animal Health Corporation , U . S . PATENT DOCUMENTS Teaneck , NJ (US ) ; Desert King 6 ,569 , 843 B1 5 /2003 Walker International LLC , San Diego , CA 2006 /0051365 A1 3 /2006 Gorenflot et al . (US ) 2008/ 0274211 AL 11/ 2008 McNeff et al. (72 ) Inventors: Kenneth W . Bafundo , Teaneck , NJ 2014 / 0037698 Al 2 / 2014 Perez (US ) ; A . Bruce Johnson , Teaneck , NJ (US ) ; David Calabotta , Teaneck , NJ FOREIGN PATENT DOCUMENTS (US ) ; Wendell Knehans , Teaneck , NJ (US ) CN 1678349 A 10 / 2005 CN 101563090 A 10 / 2009 CN 102333877 A 1 / 2012 ( 73 ) Assignees : Phibro Animal Health Corporation , EP 0 791 298 A1 8 / 1997 Teaneck , NJ (US ) ; Desert King JP 7 - 107923 4 / 1995 International LLC , San Diego , CA JP 8 - 131089 5 / 1996 H09 - 224585 9 / 1997 (US ) JP 2004 -525617 8 / 2004 ( * ) Notice : Subject to any disclaimer , the term of this WO WO 02 /052949 7 / 2002 patent is extended or adjusted under 35 WO WO 02/ 067963 9 / 2002 U . S . C . 154 (b ) by 102 days . (21 ) Appl. No. : 15 / 359, 342 OTHER PUBLICATIONS Cheeke 2009 ( Applications of saponins as feed additives in poultry ( 22 ) Filed : Nov. 22 , 2016 production — Engormix , published Dec . 3, 2009 ) ( Year: 2009 ). * Alfaro et al 2007 J . Appl . Poult . Res. 16 : 248 -254 . ( Year: 2007 ) . * (65 ) Prior Publication Data Shojadoost 2013 , The Journal of Applied Poultry Research , vol. 22 , Issue 2 , pp . 160 - 167 . ( Year : 2013 ). * US 2017 /0072002 A1 Mar. 16 , 2017 Abbas et al. , “ Botanicals : an alternative approach for the control of avian coccidiosis , ” World Poultry Science Journal, 68 (2 ) : 203 - 215 , Jun. 1 , 2012 . Related U . S . Application Data Al- Bar et al. , “ Effect of dietary Yucca shidegria extract (Deodorase ) on environmental ammonia and growth performance of chickens (63 ) Continuation - in -part of application No . and rabbits , ” Journal of Animal Science , 71( 1 ) : p . 114 , Jan . 1 , 1993 . PCT/ US2015 /032301 , filed on May 22, 2015 . Cheeke , “ Actual and potential applications of Yucca schidigera and Quillaja saponaria saponins in human and animal nutrition ,” Pro ceedings of the American Society of Animal Science , pp . 1- 10 , 1999 . (60 ) Provisional application No . 62 /002 , 527 , filed on May Cheeke , “ Actual and potential applications of Yucca schidigera and 23 , 2014 . Quillaja saponaria saponins in human and animal nutrition ,” Recent Advances in Animal Nutrition in Australia , vol. 13 , pp . 115 - 126 , (51 ) Int. Ci. 2001 . A61K 38 /05 ( 2006 .01 ) (Continued ) A6IK 38 / 15 ( 2006 .01 ) A23K 50 /00 ( 2016 . 01 ) A23K 50 / 70 ( 2016 .01 ) Primary Examiner — Padmavathi Baskar A23K 50 / 75 ( 2016 .01 ) (74 ) Attorney , Agent, or Firm — Klarquist Sparkman , A61K 39 /012 ( 2006 .01 ) LLP A61K 36 /88 ( 2006 .01 ) A61K 36 /896 ( 2006 . 01 ) (57 ) ABSTRACT A61K 36 / 73 ( 2006 . 01 ) Disclosed herein are embodiments of a combination and /or A23K 20 / 10 ( 2016 .01 ) composition for administration to animals . In some embodi A61K 31 /35 ( 2006 . 01 ) ments , the combination and/ or composition can be admin A61K 36 / 185 ( 2006 . 01 ) istered to treat and / or prevent a disease in animals . In some A61K 39 / 00 ( 2006 .01 ) embodiments , the combination and / or composition can be (52 ) U . S . CI. administered to promote animal health . In some embodi CPC ...... A61K 36 /88 (2013 . 01 ); A23K 20 / 10 ments , the combination comprises a composition comprising ( 2016 . 05 ) ; A23K 50 /00 (2016 . 05 ) ; A23K 50 / 70 Yucca schidigera , Quillaja saponaria , and combinations ( 2016 . 05 ) ; A23K 50 / 75 ( 2016 . 05 ) ; A61K 31/ 35 thereof and a composition comprising an antimicrobial, an (2013 .01 ) ; A61K 36 / 185 (2013 .01 ) ; A61K antibiotic , an anticoccidial, a vaccine , or combinations 36 / 73 ( 2013 .01 ) ; A61K 36 /896 ( 2013 .01 ) ; thereof . The combinations or compositions disclosed herein A61K 38 / 05 (2013 . 01 ) ; A61K 38 / 15 (2013 .01 ) ; can also improve feed conversion rates in animals . A61K 39 /012 (2013 .01 ) ; AKIK 2039 /552 24 Claims, 45 Drawing Sheets ( 2013 .01 ) (23 of 45 Drawing Sheet( s ) Filed in Color ) US 10 ,413 ,581 B2 Page 2

( 56 ) References Cited Patra et al. , “ Effects of quillaja and yucca saponins on communities and select populations of rumen bacteria and archaea , and fermen tation in vitro , ” Journal of Applied Microbiology , vol. 112 , pp . OTHER PUBLICATIONS 1329 - 1340 , Sep . 13 , 2012 . Cheeke et al. , “ Yucca , quillaja may have role in animal nutrition ," Rambozzi et al. , “ In vivo Anticoccidial Activity of Yucca schidigera Feedstuffs , 77 ( 3 ) : 8 pages , Jan . 17 , 2005 . Saponins in Naturally Infected Calves, ” Journal of Animal and Choi et al. , “ Enhancement of aerobic biodegradation in an oxygen Veterinary Advances , 10 ( 3 ) : 391 - 394 , 2011 . limiting environment using a saponin -based microbubble suspen sion ,” Environmental Pollution , vol. 157 , 2197 - 2202 , 2009 . Casillas -Hernández et al. , “ Evaluación de NUTRIFITOTM como Garcia et al ., “ Effect of Quillaja saponaria Extract on Passive promotor natural en el alimento , para la producción comercial del Immunization in Pig Model, ” Journal of Animal and Veterinary camarón blanco del Pacifico Litopenaeus vannamei ,” Revista Advances, 3 ( 8 ) : 535 - 541 , 2004 . Latinoamericano de Recursos Naturales 5 ( 2 ) : 174 - 179 , 2009 with Hassan et al. , “ Hemolytic and Antimicrobial Activities Differ Among English language abstract. Saponin - rich Extracts from Guar, Quillaja , Yucca , and Soybean , " Francis et al. , “ Quillaja saponins a natural growth promoter for Applied Biochemistry and Biotechnology , 162 ( 4 ) : 1008 - 1017 , Nov . fish , ” Animal Feed Science and Technology 121 :147 -157 , 2005 . 15 , 2009 . Hernández - Acosta et al. , “ The effects of Yucca schidigera and Hauptli et al. “ Feeding sows in gestation and lactation with diets Quillaja saponaria on growth performance and enzymes activities containing saponins, " Ciênc . Rural, Santa Maria , v . 36 , n . 2 , p . of juvenile shrimp Litopenaeus vannamei cultured in low - salinity 610 -616 , Mar. Apr. 2006 . water, ” Latin American Journal of Aquatic Research 44 ( 1 ) : 121 - 128 , Ilsley et al ., “ Effect of dietary supplementation of sowswith quillaja Mar . 1 , 2016 . saponins during gestation on colostrum composition and perfor Office Action issued by Japan Patent Office for Japanese Application mance of piglets suckled ,” Animal Science , 80 : 179 -184 , 2005 . No. 2017 - 514395 dated May 28 , 2019 . International Search Report and Written Opinion issued for Inter Office Action issued by Russian Patent Office for Russian Appli national Application No . PCT/ US2015 /032301 , dated Jul. 17, 2015 cation No. 2016149801 dated May 17 , 2019 . ( 11 pages ) . Santacruz - Reyes et al ., “ Efficacy of Yucca schidigera extract from Johnston et al . , “ Evaluation of DSS4 - 0 Yucca saponin on broiler performance , " Poultry Science , 59( 7 ) : 1625 , Jan . 1 , 1980 . ammonia reduction in fresh water: Effectiveness analysis and empiri Nazeer et al. , “ Effect of Yucca Saponin on Urease Activity and cal modeling approach ," Aquaculture 287 : 106 - 111 , 2009 . Development of Ascites in Broiler Chickens , ” International Journal Bafundo et al. , “ Anticoccidial Effects ofMagni -PhiTM , a Triterpenoid of Poultry Science, 1 ( 6 ) : 174 - 178 , Jun . 2002. Saponin , When Combined with Salinomycin or Used to Support the Turner et al. , “ Effects of a Quillaja saponaria extract on growth Effectiveness of a Coccidiosis Vaccine ,” Abstract and slide presen performance and immune function ofweanling pigs challenged with tation from the American Association of Avian Pathologists Meet Salmonella typhimurium , ” Journal of Animal Science , 80 : 1939 ing , Jul. 2015 . 1946 , 2002 Bafundo et al. , “ Performance and Anticoccidial Effects of Magni Vaclavkova et al. , “ Effect of Herbal Extract on Growth Parameters Phi in Coccidia - Vaccinated Broilers ,” International Poultry Scien of Weaned Piglets , ” Research in Pig Breeding , 2 ( 2 ) : 36 - 38 , 2008 . tific Forum , p . 10 , Jan . 2016 . Veit et al. , “ Effects of phytogenic feed additives containing Quillja Bafundo et al. , “ The effects of Nutrafito Plus and virginiamycin on saponaria on ammonia in fattening pigs ,” Proceedings of the XVth the performance and anticoccidial responses of broilers vaccinated International Congress of the International Society for Animal for coccidiosis, ” Poultry Sci . 93 : ( E - Suppl. 1 ) p . 41. Jul. 2014 . Hygiene, Vienna , Austria , Jul. 3 -7 , 2011 , vol. 3 2011 pp . 1255 - 1257 . Espejo Marquinez “ Evaluación experimental de las saponinas del Zhao , “Mechanisms of quorum sensing and strategies for quorum quillay ( Quillaja saponaria ) como inhibidora del desarrollo de sensing disruption in aquaculture pathogens, ” Journal of Fish coccidias intestinales en pollos de engorda ,” Thesis , Universidad de Diseases, 38 ( 9 ): 771 -786 , Sep . 15 , 2014 . Chile , availability date of Jul. 2 , 2015 . Yeo et al . , “ Effect of Feeding Diets Containing an Antibiotic , a Hassan , S . M . Antimicrobial activities of saponin - rich guar meal Probiotic, or Yucca Extract on Growth and Intestinal Urease Activ extract. Ph . D . Thesis, Texas A & M University , May 2008 . ity in Broiler Chicks, ” Poultry Science, 76 (2 ): 381 - 385 , Mar. 1997 . Johnson et al. , “ Anticoccidial Drugs : Lesion Scoring Techniques in Naknukool et al ., “ Stimulating Macrophage Activity in Mice and Battery and Floor- Pen Experiments with Chickens, ” Experimental Humans by Oral Administration of Quillaja Saponin , ” Biosci. Parasitology , 28 ( 1 ) : 30 -36 , Aug . 1970 . Biotechnol. Biochem ., 75 ( 10 ): 18891893, Oct . 7, 2011. Scheurer , et al. , “ Effect of 3 dietary phytogenic products on pro Alfaro et al ., “ Use of Yucca schidigera extract in broiler diets and duction performance and coccidiosis in challenged broiler chick its effect on performance results obtained with different coccidosis ens, " J . Appl . Poult. Res. 22 : 591 -599 , Oct . 1 , 2013 . control methods, " Journal of Applied Poultry Research , 16 ( 2 ) : Sen , S . , H . P . S . Makkar , S . Muetzel, and K . Becker. Effect of 248 - 254 , Jul. 1 , 2007 . Quillaja saponaria saponins and Yucca schidigera plant extracts on Cheeke et al. , “ Applications of saponins as feed additives in poultry growth of Escherichia coli . Lett . Appl . Microbiol. 27 : 35 - 38 . Jul. production ,” 20th Annual Australian Poultry Science Symposium , 1998 . pp . 50 - 55 , Feb . 9 - 11 , 2009 Sparg et al. , “ Biological activities and distribution of plant saponins, " Office Action issued for Russian Application No . 2016149801 , Journal of Ethnopharmacology , 94 (2 - 3 ): 219 -243 , Oct . 2004 . dated Nov . 14 , 2018 . Johnston et al. , “ Broiler Performance with Dss40 Yucca Saponin in Office Action issued for Israeli Application No. 249061 , dated Dec. Combination with Monensin ,” Poultry Science , 61 (6 ) : 1052 -1054 , 20 , 2018 . Jun . 1982 . Grabensteiner et al. , “ Differences in the in vitro susceptibility of Yuan et al. , “ World Medicinal Botanicals , ” p . 312 , Jan . 31, 2012 . mono -eukaryotic cultures of Histomonas meleagridis , Tetratrichomonas Wang , " Cosmetic Plant Materials, " p . 353 , Jun . 30 , 2012 . gallinarum and Blastocystis sp . to natural organic compounds, " Office Action and Search Report issued by the Chinese National Parasitol Res ., vol. 101, pp . 193 - 199 , Feb . 7 , 2007 . Intellectual Property Administration for Chinese Application No. McAllister et al ., “ Studies on the use of Yucca schidigera to control 201580035572 .6 dated Jan . 18 , 2019 . giardiasis ,” Veterinary Parasitology , vol. 97 , pp . 85 - 99 , May 11 , 2001. * cited by examiner U . S . Patent Sep. 17 , 2019 Sheet 1 of 45 US 10 ,413 ,581 B2

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37 kud Score Fecal Mean U . S . Patent Sep. 17 , 2019 Sheet 27 of 45 US 10 ,413 ,581 B2

V 250PPMComposition a1000PPMComposition

FIG.49 DayofAge PositiveControl &750ppm Composition

13 NegativeControl 500ppm Composition

1 Score Lesion Mean U . S . Patent Sep. 17, 2019 Sheet 28 of 45 US 10 ,413 ,581 B2

16 250PPMComposition *1000PPMComposition DayofAge FIG.50 PositiveControl 750ppm Composition

13 aNegativeControl 500ppm Composition

3 1 Score Lesion Mean - U . S . Patent Sep. 17 , 2019 Sheet 29 of 45 US 10 ,413 ,581 B2

250PPMComposition 01000PPMComposition DayofAge PositiveControl FIG.51 *750ppm Composition

13 NegativeControl 500ppm Composition

Score3 Lesion Mean atent Sep . 17 , 2019 Sheet 30 of 45 US 10 ,413 ,581 B2

PHIsamples by Day Unweighted DOO D03 DO7 PC2 .

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Lactobacillus ;reuteri Lactobacillus reuteri

MMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMM We 600 400 OriginalAbundance 200 NormalizaAbundance 0 200 400 TTTTT Composition Standard Composition Standard FIG . 54 FIG . 55 Clostridium Clostridium

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SANAA Composition Standard Composition Standard FIG , 56 FIG . 57 U . S . Patent Sep . 17 , 2019 Sheet 32 of 45 US 10 ,413 ,581 B2

Cyanobacteria . Streptophyta Cyanobacteria .. . ; Streptophyta

200 100 madadaaaaaaaaaaaaaaaaaaaaaamemangnames

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W OriginalAbundance YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY NormalizedAbundanga

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Streptococcus Streptococcus 12 2000 10

8 5001000 6 OriginalAbundance 4 NormalizedAbundance XXX 0 2

0 -1000 Composition Standard Composition Standard FIG . 62 FIG . 63 Lactobacillus , reuteri Lactobacillus reuteri

OriginalAbundance NormalizedAbundance

Composition Standard Composition Standard FIG . 64 FIG . 65 U . S . Patent Sep . 17 , 2019 Sheet 34 of 45 US 10 ,413 ,581 B2

Peptostreptococcaceae Peptostreptococcaceae

30

2

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Corynebacterium Corynebacterium

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Streptococcus Streptococcus

OriginalAbundance NormalizedAbundance

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Candidatus Arthromitus Candidatus Arthromitus

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Candidatus Arthromitus Candidatus Arthromitus

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Enterobacteriaceae Enterobacteriaceae 600 400 200 wwwwwwwwwwww OriginalAbundance 0 NormalizedAbundance 200

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FIG . 82 FIG . 83 Staphylococcus Staphylococcus 1500

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Peptostreptococcaceae Peptostreptococcaceae

200 150 Wow 100 OriginalAbundance LULU NormalizedAbundance | 50 0 TH -50 Composition Standard Composition Standard FIG . 86 FIG . 87

Enterobacteriaceae Enterobacteriaceae 150

100

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Enterococcus cecorum Enterococcus , cecorum

200250

150 OriginalAbundance 100 NormalizedAbundance 50 menorrerererererererererererere

0

50 Composition Standard Composition Standard FIG . 90 FIG . 91 Lactobacillus ,reuteri Lactobacillus reuteri

10 OriginalAbundance 8001000 NormalizedAbundance 200400600

0 Composition Standard Composition Standard FIG . 92 FIG . 93 U . S . Patent Sep. 17 , 2019 Sheet 41 of 45 US 10 ,413 ,581 B2

W w 2000 abundance 600 TTT 500 Composition PreFeed Standard FIG . 94 abundance Composition PreFeed Standard FIG . 95 U . S . Patent Sep. 17, 2019 Sheet 42 of 45 US 10 ,413 , 581 B2

abundance Composition PreFeed Standard FIG . 96

abundance LI Compositionof PreFeed Standard FIG . 97 U . S . Patent Sep . 17, 2019 Sheet 43 of 45 US 10 ,413 ,581 B2

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * 1200 - abundance 1000 200 V V V V V V V V V V Composition PreFeed Standard FIG . 98 abundance Composition PreFeed Standard FIG . 99 U . S . Patent Sep . 17 , 2019 Sheet 44 of 45 US 10 ,413 , 581 B2

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AlphaDiversity(Shannon)byTreatment AlphaDiversity(Shannon)byTreatment TTTTTT Tivi

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Composition Standard Composition Standard FIG . 108 FIG . 109 US 10 ,413 ,581 B2 COMBINATION , COMPOSITION , AND Eimeria maxima, Eimeria tenella , Eimeria mitis, Eimeria METHOD OF ADMINISTERING THE necatrix , Eimeria praecox , Eimeria brunetti , Eimeria COMBINATION OR COMPOSITION TO hagani , or combinations thereof. ANIMALS In some embodiments , the first and second compositions, 5 and optionally the third composition , are admixed to form an CROSS REFERENCE TO RELATED admixed composition . The compositions may be mixed APPLICATION simultaneously or sequentially. The admixed composition may be further admixed with a feedstuff to form a feedstuff This application is a continuation - in -part of International admixture . Application No. PCT/ US2015 / 032301, filed on May 22 , 10 The combination may be formulated for administration to 2015 , which in turn claims the benefit of the earlier filing an avian . In some embodiments , the combination is formu date of U . S . Provisional Application No . 62 / 002, 527 , filed lated for administration to chickens and turkey. In some May 23 , 2014 . These prior applications are incorporated other embodiments the combination is formulated for herein by reference in their entirety . administration to animals other than chicken or turkeys. 15 The components of the admixed composition , the feed FIELD stuff admixture , or both , may be sized , concentrated , or diluted to facilitate admixing , facilitate administration to an This disclosure concerns embodiments of a combination animal, or combinations thereof. The combination may and / or composition for administration to animals , as well as further comprise a vitamin , a trace mineral, a bulking agent, methods ofmaking the combination and /or composition and 20 a carrier , a colorant, a taste enhancer , or any combination administering the same to animals . thereof , and in some embodiments the combination further comprises corn , soybean meal, wheat, barley, rye , canola , BACKGROUND corn oil , limestone , salt, distillers dried grains with solubles (DDGS ) , dicalcium phosphate , sodium sesquicarbonate , Feed conversion rates or ratios (FCR ) provide animal 25 methionine source , lysine source , L - threonine , choline , or producers a method for monitoring the efficiency of raising any combination thereof. animals . Estimating the amount of feed required per unit of Also disclosed herein is a method, comprising adminis body gain for animals provides the animal producers the tering the composition and / or combinations described ability to effectively budget costs associated with raising the herein . In some embodiments , themethod further comprises animals . Feed conversion rates also can be used to reduce 30 administering a third composition comprising a coccidiosis risks associated with raising animals , such as feed shortfalls vaccine comprising oocysts derived from Eimeria acervu or waste , and can facilitate determining profit margins. lina , Eimeria mivati , Eimeria maxima, Eimeria tenella , Coccidiosis is a parasitic disease of the intestinal tract of Eimeria mitis , Eimeria necatrix , Eimeria praecox , Eimeria animals caused by coccidian protozoa of the genus Eimeria . brunetti, Eimeria hagani, or combinations thereof. The first The disease can spread amongst animals by contact with 35 and second compositions , and the third composition and / or infected feces by means of an infective form called the feedstuff if present, may be administered substantially oocyst. Coccidiosis is a significant disease of certain ani- simultaneously , or they may be administered sequentially , in mals , such as domestic fowl and livestock , as it can affect any order. animals at a very young age . It can be fatal or compromise Additionally disclosed is a method for making a combi animal health , thereby impairing the feed conversion rate of 40 nation , comprising providing a first composition comprising the animals . Thus, production , reproductive efficiency and Quillaja saponaria , Yucca schidigera , or both ; providing a animal health are adversely affected by coccidiosis . Dis second composition comprising an antimicrobial agent, an eases , such as coccidiosis , cause significant economic losses antibiotic , an anticoccidial agent, or a combination thereof ; in certain animal industries . Such diseases also can nega - and mixing the first composition and the second composi tively affect the health of domesticated animals . 45 tion . The method may further comprise admixing the com bination with a feedstuff to form an admixed feedstuff . In SUMMARY some embodiments , the method further comprises formu lating the first and / or second compositions for mixture with Disclosed herein are embodiments of a combination com the feedstuff to provide a substantially homogeneous prising a first combination comprising Yucca , Quillaja , or 50 admixed feedstuff . both ; and a second composition comprising an antibiotic , an In certain embodiments, the method further comprises antimicrobial, an anticoccidial agent , or a combination combining the first composition , the second composition , or thereof. In some embodiments , the combination comprises both with a third composition comprising a vaccine. 200 ppm to 5 , 000 ppm of a first composition comprising The foregoing and other objects , features , and advantages Quillaja saponaria , Yucca schidigera , or a combination 55 of the present disclosure will become more apparent from thereof, and a second composition comprising an antimicro - the following detailed description , which proceeds with bial, an antibiotic , an anticoccidial agent, or combinations reference to the accompanying figures. thereof. The second composition may comprise 10 ppm to 30 ppm Virginiamycin and /or 50 ppm to 70 ppm Salinomy BRIEF DESCRIPTION OF THE DRAWINGS cin . In some embodiments , the first composition can com - 60 prise a mixture of Quillaja saponaria and Yucca schidigera The patent or application file contains at leastone drawing in a ratio ranging from 70 : 30 Quillaja saponaria : Yucca executed in color. Copies of this patent or patent application schidigera to 90 : 10 Quillaja saponaria : Yucca schidigera publication with color drawing( s ) will be provided by the Embodiments of the combinations may also include a Office upon request and payment of the necessary fee . third composition comprising a vaccine , and in some 65 FIG . 1 is a graph of average weight (kg ) and adjusted feed embodiments , the vaccine is a composition comprising conversion of birds fed for 28 days with bird feed ( Treat oocysts derived from Eimeria acervulina , Eimeria mivati , ment Group 1 ), and bird feed comprising 125 ppm of an US 10 ,413 , 581 B2 embodiment of a composition according to the present different feed combinations comprising Oppm , 200 ppm , or disclosure (composition embodiment ( Treatment Group 2 ) , 250 ppm of a composition embodiment, and /or 0 ppm or 22 250 ppm of the same composition embodiment ( Treatment ppm Virginiamycin . Group 3 ) , 500 ppm of the same composition embodiment FIG . 12 is a graph of feed conversion rates illustrating ( Treatment Group 4 ), and 2 ,500 ppm of the same compo - 5 results obtained 28 days after feeding vaccinated birds with sition embodiment ( Treatment Group 5 ) . different feed combinations comprising 0 ppm , 200 ppm , or FIG . 2 is a graph of average weight (kg ) and adjusted feed 250 ppm of a composition embodiment , and / or 0 ppm or 22 conversion obtained from birds fed for 28 -42 days with bird ppm Virginiamycin . feed ( Treatment Group 1 ), and bird feed comprising 125 FIG . 13 is a graph of feed conversion rates illustrating ppm of a composition embodiment ( Treatment Group 2 ) , 10 results obtained 42 days after feeding vaccinated birds with 250 ppm of a composition embodiment ( Treatment Group different feed combinations comprising 0 ppm , 200 ppm , or 3 ) , 500 ppm of a composition embodiment (Treatment 250 ppm of a composition embodiment, and /or 0 ppm or 22 Group 4 ) , and 2 ,500 ppm of a composition embodiment ppm Virginiamycin . ( Treatment Group 5 ) . FIG . 14 is a graph of body weight gain illustrating results FIG . 3 is a graph of average weight (kg ) and adjusted feed obtained 18 days after feeding vaccinated birds with differ conversion obtained from birds fed for 42 days with bird ent feed combinations comprising 0 ppm , 200 ppm , or 250 feed ( Treatment Group 1) , and bird feed comprising 125 ppm of a composition embodiment, and /or 0 ppm or 22 ppm ppm of a composition embodimentliment ( Treatment Group 22 )) ., Virginiamycin . 250 ppm of a composition embodiment ( Treatment Group 20 FIG . 15 is a graph of body weight gain illustrating results 3 ) , 500 ppm of a composition embodiment ( Treatment obtained 28 days after feeding vaccinated birds with differ Group 4 ), and 2 ,500 ppm of a composition embodiment ent feed combinations comprising 0 ppm , 200 ppm , or 250 ( Treatment Group 5 ) . ppm of a composition embodiment, and /or 0 ppm or 22 ppm FIG . 4 is a graph of bird weight gain (kg ) illustrating Virginiamycin . results obtained from feeding birds various different treat- 25 FIG . 16 is a graph of body weight gain illustrating results ments of a composition embodiment ( 0 ppm , 150 ppm , 200 obtained 42 days after feeding vaccinated birds with differ ppm , and 250 ppm ) and Virginiamycin ( 0 ppm and 22 ppm ) , ent feed combinations comprising 0 ppm , 200 ppm , or 250 with the graph providing results obtained after 18 days of ppm of a composition embodiment, and /or 0 ppm or 22 ppm feeding. Virginiamycin . FIG . 5 is a graph of bird weight gain (kg ) illustrating 30 FIG . 17 is a graph of oocysts per gram of feces illustrating results obtained from feeding birds various different treat - results obtained 21 days after feeding vaccinated birds with ments of a composition embodiment (0 ppm , 150 ppm , 200 different feed combinations comprising 0 ppm , 200 ppm , or ppm , and 250 ppm ) and Virginiamycin (0 ppm and 22 ppm ) 250 ppm of a composition embodiment, and /or 0 ppm or 22 with the graph providing results obtained after 18 - 32 days of ppm Virginiamycin . feeding . 35 FIG . 18 is a graph of lesion scores post challenge illus FIG . 6 is a graph of bird weight gain (kg ) illustrating trating results obtained 21 - 28 days after feeding vaccinated results obtained from feeding birds various different treat birds with different feed combinations comprising 0 ppm , ments of a composition embodiment ( 0 ppm , 150 ppm , 200 200 ppm , or 250 ppm of a composition embodiment, and /or ppm , and 250 ppm ) and Virginiamycin ( 0 ppm and 22 ppm ), Oppm or 22 ppm Virginiamycin . with the graph providing results obtained after 0 -32 days of 40 FIG . 19 is a graph of lesion scores post challenge illus feeding. trating results obtained 28 days after feeding vaccinated FIG . 7 is a graph of bird weight gain (kg ) illustrating birds with different feed combinations comprising 0 ppm , results obtained from feeding birds various different treat - 200 ppm , or 250 ppm of a composition embodiment, and /or ments of a composition embodiment ( 0 ppm , 150 ppm , 200 Oppm or 22 ppm Virginiamycin , wherein the results were ppm , and 250 ppm ) and Virginiamycin (0 ppm and 22 ppm ), 45 pooled across Virginiamycin levels . with the graph providing results obtained after 32 days of FIG . 20 is a graph of adjusted feed conversion illustrating feeding . results obtained 18 days after feeding birds with different FIG . 8 is a graph of bird weight gain ( kg ) illustrating combinations comprising a composition embodiment (0 results obtained from feeding birds various different treat- ppm and 250 ppm ) and /or Salinomycin ( 0 ppm and 66 ppm ) . ments of a composition embodiment ( 0 ppm , 150 ppm , 200 50 FIG . 21 is a graph of adjusted feed conversion illustrating ppm , and 250 ppm ) and Virginiamycin ( 0 ppm and 22 ppm ), results obtained 28 days after feeding birds with different with the graph providing results obtained after 32 -42 days of combinations comprising a composition embodiment ( 0 feeding. ppm and 250 ppm ) and / or Salinomycin ( 0 ppm and 66 ppm ) . FIG . 9 is a graph of bird weight gain (kg ) illustrating FIG . 22 is a graph of adjusted feed conversion illustrating results obtained from feeding birds various different treat- 55 results obtained 42 days after feeding birds with different ments of a composition embodiment ( 0 ppm , 150 ppm , 200 combinations comprising a composition embodiment ( 0 ppm , and 250 ppm ) and Virginiamycin ( 0 ppm and 22 ppm ) , ppm and 250 ppm ) and / or Salinomycin ( 0 ppm and 66 ppm ). with the graph providing results obtained after 0 - 42 days of FIG . 23 is a graph of body weight gain illustrating results feeding . obtained 18 days after feeding birds with different combi FIG . 10 is a graph of bird weight gain (kg ) illustrating 60 nations comprising a composition embodiment ( 0 ppm and results obtained from feeding birds various different treat - 250 ppm ) and / or Salinomycin ( 0 ppm and 66 ppm ) . ments of a composition embodiment ( 0 ppm , 150 ppm , 200 FIG . 24 is a graph of body weight gain illustrating results ppm , and 250 ppm ) and Virginiamycin (0 ppm and 22 ppm ), obtained 28 days after feeding birds with different combi with the graph providing results obtained after 42 days of nations comprising a composition embodiment (0 ppm and feeding. 65 250 ppm ) and / or Salinomycin ( 0 ppm and 66 ppm ) . FIG . 11 is a graph of feed conversion rates illustrating FIG . 25 is a graph of body weight gain illustrating results results obtained 18 days after feeding vaccinated birds with obtained 42 days after feeding birds with different combi US 10 ,413 ,581 B2 nations comprising a composition embodiment ( 0 ppm and vaccine and fed 0 mg or 250 mg of a composition embodi 250 ppm ) and / or Salinomycin ( 0 ppm and 66 ppm ) . ment for days ( - 42 , days 0 - 28 , days 29 -42 , and days 19 -42 . FIG . 26 is a graph of oocysts per gram of feces illustrating FIG . 41 is a graph of body weight gain illustrating the results obtained 28 days after feeding vaccinated birds with effects of a composition embodiment on birds vaccinated different feed combinations comprising a composition 5 with a coccidiosis vaccine at birth wherein the results embodiment (0 ppm and 250 ppm ) and /or Salinomycin 0 illustrated are for birds that were not fed the composition ppm and 66 ppm ). embodiment ( left bar ) and for birds that were fed the FIG . 27 is a graph of lesion scores post challenge illus trating results obtained 28 days after feeding vaccinated composition for different time periods ( right bar ); the results birds with different feed combinations comprising O ppm , 10 were measured at day 18 . 200 ppm , or 250 ppm of a composition embodiment and /or FIG . 42 is a graph of body weight gain illustrating the O ppm or 22 ppm Virginiamycin . effects of a composition embodiment on birds vaccinated FIG . 28 is a graph of oocysts per gram of feces illustrating with a coccidiosis vaccine at birth wherein the results results on day 18 for birds fed (a ) salinomycin and 250 mg illustrated are for birds that were not fed the composition of a composition embodiment or (b ) salinomycin alone . 15 embodiment€ (left bar) and for birds that were fed the FIG . 29 is a graph of oocysts per gram of feces illustrating composition for different time periods ( right bar ) ; the results results on day 28 for birds fed salinomycin and 250 mg of were measured at day 28 . a composition embodiment for days 0 -42 , days 0 - 28 , days FIG . 43 is a graph of body weight gain illustrating results 29 -42 , and days 19 - 42 . on day 42 for birds administered a coccidiosis vaccine and FIG . 30 is a graph of adjusted feed conversion illustrating 20 fed 0 mg or 250 mg of a composition embodiment for days results on day 18 for birds fed salinomycin and 250 mg of 0 -42 , days 0 - 28 , days 29 - 42 , and days 19 -42 . a composition embodiment for days 0 -42 , days 0 - 28, days FIG . 44 is a graph of oocysts per gram of feces illustrating 29 - 42 , and days 19 -42 . results on day 18 for birds administered a coccidiosis FIG . 31 is a graph of adjusted feed conversion illustrating vaccine and fed 0 mg or 250 mg of a composition embodi results on day 28 for birds fed salinomycin and 250 mg of 25 ment for days 0 -42 , days 0 - 28 , days 29 - 42 , and days 19 -42 . a composition embodiment for days 0 - 42 , days 0 - 28 , days FIG . 45 is a graph of oocysts per gram of feces illustrating 29 - 42 , and days 19 -42 . results on day 28 for birds administered a coccidiosis FIG . 32 is a graph of adjusted feed conversion illustrating vaccine and fed 0 mg or 250 mg of a composition embodi results on day 42 for birds fed salinomycin and 250 mg of ment for days 0 -42 , days 0 - 28 , days 29 -42 , and days 19 -42 . a composition embodiment for days 0 -42 , days 0 - 28 , days 30 EL 29 -42 , and days 19 -42 . FIG . 46 is a graph of body weight versus age in days , FIG . 33 is a graph of adjusted feed conversion illustrating illustrating the different changes in body weight for the results on days 29 -42 for birds fed salinomycin and 250 mg5 different treatment groups over time. of a composition embodiment for days 0 - 42, days 0 - 28 , days FIG . 47 is a graph of mean trophozoite score versus age 29 -42 , and days 19 -42 . 35 in days, illustrating a general dose dependent reduction of FIG . 34 is a graph of body weight gain (kg ) illustrating trophozoite score for groups administered a composition results on day 18 for birds fed salinomycin and 250 mg of comprising Quillaja saponaria and Yucca schidigera . a composition embodiment for days 0 - 42 , days 0 - 28 , days FIG . 48 is a graph ofmean fecal score versus age in days, 29 - 42 , and days 19 - 42 . illustrating the different amounts of enteritis detected in FIG . 35 is a graph of body weight gain (kg ) illustrating 40 fecal samples for the different treatment groups over time . results on day 28 for birds fed salinomycin and 250 mg of FIG . 49 is a graph ofmean lesion score versus age in days , a composition embodiment for days 0 -42 , days 0 - 28 , days illustrating the duodenal lesion score for the different treat 29 -42 , and days 19 - 42 . ment groups at days 13 and 16 . FIG . 36 is a graph of body weight gain (kg ) illustrating FIG . 50 is a graph of mean lesion score versus age in days , results on day 42 for birds fed salinomycin and 250 mg of 45 illustrating the jejunal lesion score for the different treatment a composition embodiment for days 0 - 42 , days 0 - 28 , days groups at days 13 and 16 . 29 - 42 , and days 19 - 42 . FIG . 51 is a graph ofmean lesion score versus age in days , FIG . 37 is a graph of body weight gain (kg ) illustrating illustrating the ileal lesion score for the different treatment results on days 29 - 42 for birds fed salinomycin and 250 mg groups at days 13 and 16 . of a composition embodiment for days 0 -42 , days 0 - 28 , days 50 FIG . 52 is a PCOA plot colored by age, illustrating the 29 -42 , and days 19 -42 . age -dependent progression of the bacterial community in the FIG . 38 is a graph of adjusted feed conversion illustrating gut of the turkeys. the effects of a composition embodiment on birds vaccinated FIG . 53 is a PCoA plot colored by treatment, illustrating with a coccidiosis vaccine at birth wherein the results the differences between the bacterial communities between illustrated are for birds that were not fed the composition 55 control and treatment groups. embodiment ( left bar ) and for birds that were fed the FIG . 54 is a plot of original abundance illustrating the composition for different time periods ( right bar ) ; the results amount of Lactobacillus reuteri in the control and treatment were measured at day 18 . groups at day 3 . FIG . 39 is a graph of adjusted feed conversion illustrating FIG . 55 is a plot of normalized abundance illustrating the the effects of a composition embodiment on birds vaccinated 60 amount of Lactobacillus reuteri in the control and treatment with a coccidiosis vaccine at birth wherein the results groups at day 3 . illustrated are for birds that were not fed the composition FIG . 56 is a plot of original abundance illustrating the embodiment (left bar ) and for birds that were fed the amount of Clostridium species in the control and treatment composition for different time periods ( right bar ) ; the results groups at day 3 . were measured at day 28 . 65 FIG . 57 is a plot of normalized abundance illustrating the FIG . 40 is a graph of adjusted feed conversion illustrating amount of Clostridium species in the control and treatment results on day 42 for birds administered a coccidiosis groups at day 3 . US 10 ,413 ,581 B2 FIG . 58 is a plot of original abundance illustrating the FIG . 80 is a plot of original abundance illustrating the amount of cyanobacterial sequences in the control and amount of Corynebacterium species in the control and treatment groups at day 7 . treatment groups at day 32 . FIG . 59 is a plot of normalized abundance illustrating the FIG . 81 is a plot of normalized abundance illustrating the amount of cyanobacterial sequences in the control and 5 amount of Corynebacterium species in the control and treatment groups at day 7 . treatment groups at day 32. FIG . 60 is a plot of original abundance illustrating the FIG . 82 is a plot of original abundance illustrating the amount of Enterococcus species in the control and treatment amount of E . coli in the control and treatment groups at day groups at day 7 . 32 . FIG . 61 is a plot of normalized abundance illustrating the 10 FIG . 83 is a plot of normalized abundance illustrating the amount of Enterococcus species in the control and treatment amount of E . coli in the control and treatment groups at day groups at day 7. 32 . FIG . 62 is a plot of original abundance illustrating the FIG . 84 is a plot of original abundance illustrating the amount of Streptococcus species in the control and treatment 15 amount of Staphylococcus species in the control and treat groups at day 7 . ment groups at day 32 . FIG . 63 is a plot of normalized abundance illustrating the FIG . 85 is a plot of normalized abundance illustrating the amount of Streptococcus species in the control and treatment amount of Staphylococcus species in the control and treat groups at day 7 . ment groups at day 32 . FIG . 64 is a plot of original abundance illustrating the 20 FIG . 86 is a plot of original abundance illustrating the amount of Lactobacillus reuteri in the control and treatment amount of Peptostreptococcaceae in the control and treat groups at day 14 . ment groups at day 32 . FIG . 65 is a plot of normalized abundance illustrating the FIG . 87 is a plot of normalized abundance illustrating the amount of Lactobacillus reuteri in the control and treatment amount of Peptostreptococcaceae in the control and treat groups at day 14 . 25 ment groups at day 32 . FIG . 66 is a plot of original abundance illustrating the FIG . 88 is a plot of original abundance illustrating the amount of Peptostreptococcaceae in the control and treat - amount of E . coli in the control and treatment groups at day ment groups at day 14 . 84 . FIG . 67 is a plot of normalized abundance illustrating the FIG . 89 is a plot of normalized abundance illustrating the amount of Peptostreptococcaceae in the control and treat - 30 amount of E . coli in the control and treatment groups at day ment groups at day 14 . 0484 . FIG . 68 is a plot of original abundance illustrating the FIG . 90 is a plot of original abundance illustrating the amountof Clostridiaceae in the control and treatment groups amount of Enterococcus cecorum in the control and treat at day 21. ment groups at day 84 . FIG . 69 is a plot of normalized abundance illustrating the 35 FIG . 91 is a plot of normalized abundance illustrating the amount of Clostridiaceae in the control and treatment groups amount of Enterococcus cecorum in the control and treat at day 21 . ment groups at day 84 . FIG . 70 is a plot of original abundance illustrating the FIG . 92 is a plot of original abundance illustrating the amount of Corynebacterium species in the control and amount of Lactobacillus reuteri in the control and treatment treatment groups at day 21 . 40 groups at day 84 . FIG . 71 is a plot of normalized abundance illustrating the FIG . 93 is a plot of normalized abundance illustrating the amount of Corynebacterium species in the control and amount of Lactobacillus reuteri in the control and treatment treatment groups at day 21 . groups at day 84 . FIG . 72 is a plot of original abundance illustrating the FIG . 94 is a plot of abundance versus treatment illustrat amount of Staphylococcus species in the control and treat- 45 ing the amount of E . coli detected at day 3 . ment groups at day 21 . FIG . 95 is a plot of abundance versus treatment illustrat FIG . 73 is a plot of normalized abundance illustrating the ing the amount of E . coli detected at day 7 . amount of Staphylococcus species in the control and treat - FIG . 96 is a plot of abundance versus treatment illustrat ment groups at day 21 . ing the amount of E . coli detected at day 14 . FIG . 74 is a plot of original abundance illustrating the 50 FIG . 97 is a plot of abundance versus treatment illustrat amount of Streptococcus species in the control and treatment ing the amount of E . coli detected at day 21 . groups at day 21. FIG . 98 is a plot of abundance versus treatment illustrat FIG . 75 is a plot of normalized abundance illustrating the ing the amount of E . coli detected at day 32 . amount of Streptococcus species in the control and treatment FIG . 99 is a plot of abundance versus treatment illustrat groups at day 21. 55 ing the amount of E . coli detected at day 84 . FIG . 76 is a plot of original abundance illustrating the FIG . 100 is a plot of abundance versus treatment illus amount of Candidatus Arthromitus in the control and treat - trating the difference in the amount of Candidatus Arthro ment groups at day 21 . mitus detected between the control and treatment groups . FIG . 77 is a plot of normalized abundance illustrating the FIG . 101 is a plot of abundance versus treatment illus amount of Candidatus Arthromitus in the control and treat- 60 trating the difference in the amount of Candidatus Arthro ment groups at day 21 . mitus detected between the control and treatment groups. FIG . 78 is a plot of original abundance illustrating the FIG . 102 is a plot of abundance versus treatment illus amount of Candidatus Arthromitus in the control and treat- trating the difference in the amount of Candidatus Arthro ment groups at day 32 . mitus detected between the control and treatment groups . FIG . 79 is a plot of normalized abundance illustrating the 65 FIG . 103 is a plot of abundance versus treatment illus amount of Candidatus Arthromitus in the control and treat- trating the difference in the amount of Candidatus Arthro mentm groups at day 32 . mitus detected between the control and treatment groups . US 10 ,413 ,581 B2 10 FIG . 104 is a plot of diversity versus treatment, illustrat - To facilitate review of the various embodiments of the ing the bacterial community diversity of the control and disclosure , the following explanations of specific terms are treatment groups at day 3 . provided : FIG . 105 is a plot of diversity versus treatment, illustrat - Administering: Providing a combination , composition , or ing the bacterial community diversity of the control and 5 component disclosed herein by any suitable route to an treatment groups at day 7 . animal . In some embodiments disclosed herein , administra FIG . 106 is a plot of diversity versus treatment, illustrat - tion can refer to oral administration . ing the bacterial community diversity of the control and Animal: This term includes , but is not limited to , humans , treatment groups at day 14 . mammals , aquaculture species , and avian species. In some FIG . 107 is a plot of diversity versus treatment, illustrat - embodiments , this term can refer to mammals , aquaculture ing the bacterial community diversity of the control and species, and avian species that are raised for human con treatment groups at day 21. sumption or that are domesticated animals . Exemplary such FIG . 108 is a plot of diversity versus treatment, illustrat - animal species are provided herein . ing the bacterial community diversity of the control and 15 Aquaculture Species : An animal that lives in salt or fresh treatment groups at day 32 . water . Exemplary aquaculture species are disclosed herein . FIG . 109 is a plot of diversity versus treatment, illustrat- Binding agent or binder: A material or substance that is ing the bacterial community diversity of the control and used to hold or draw together other materials to form a treatment groups at day 84 . cohesive unit . Examples include , but are not limited to , 20 acacia , alginic acid , carboxymethylcellulose, sodium com DETAILED DESCRIPTION pressible sugar , ethylcellulose gelatin , liquid glucose , meth ylcellulose , povidone or pregelatinized starch . This disclosure concerns embodiments of a combination Co- administration : Administering two or more combina comprising Quillaja ( e . g ., Quillaja saponaria ) , Yucca ( e . g ., tions, compositions, or components simultaneously or Yucca schidigera ), an antimicrobial, an antibiotic , an antic - 25 sequentially in any order to a subject to provide overlapping occidial agent, and /or a vaccine , such as a coccidiosis periods of time in which the subject is experiencing effects , vaccine. Methods of administering the combination and /or beneficial and / or deleterious, from each component. One or composition embodiments disclosed herein are described , as more of the components may be a therapeutic agent. Com are methods for treating and /or preventing certain diseases, ponents may be combined into a single composition or such as coccidiosis , in animals using embodiments of the 30 dosage form , or they may be administered as separate disclosed combination and / or composition embodiments . components either simultaneously or sequentially in any order . When administered sequentially , the two or more I . Terms and Definitions components are administered within an effective period of time to provide overlapping periods of time in which the The following explanations of termsand abbreviations are 35 subject experiences effects from each component. provided to better describe the present disclosure and to Combination : A combination comprises two or more guide those of ordinary skill in the art in the practice of the compositions or components that are administered such that the effective time period of the first composition or compo present disclosure . As used herein , “ comprising ” means nent overlaps with the effective time period of the second “ including ” and the singular forms “ a ” or “ an ” or “ the ” 40 and subsequent compositions or components. A combination include plural references unless the context clearly dictates may be a composition comprising the components , or it may otherwise. The term “ or” refers to a single element of stated be two or more individual components administered sub alternative elements or a combination of two or more stantially simultaneously or sequentially in any order. elements , unless the context clearly indicates otherwise . Excipient or carrier : A physiologicallú inert substance that Unless explained otherwise , all technical and scientific 45 is used as an additive in ( or with ) a combination , composi terms used herein have the same meaning as commonly tion , or component as disclosed herein . As used herein , an understood to one of ordinary skill in the art to which this excipient or carrier may be incorporated within particles of disclosure belongs. Although methods and materials similar a combination , composition , or component, or it may be or equivalent to those described herein can be used in the physically mixed with particles of a combination , compo practice or testing of the present disclosure , suitable meth - 50 sition , or component. An excipient or carrier can be used , for ods and materials are described below . The materials , meth - example , to dilute an active agent and / or to modify proper ods , and examples are illustrative only and not intended to ties of a combination or composition . Examples of excipi be limiting. Other features of the disclosure are apparent e nts and carriers include but are not limited to calcium from the following detailed description and the claims. carbonate , polyvinylpyrrolidone (PVP ) , tocopheryl polyeth Unless otherwise indicated , all numbers expressing quan - 55 ylene glycol 1000 succinate ( also known as vitamin E tities of components , molecular weights , percentages, tem - TPGS , or TPGS) , dipalmitoyl phosphatidyl choline (DPPC ) , peratures , times , and so forth , as used in the specification or trehalose , sodium bicarbonate , glycine, sodium citrate , and claims are to be understood as being modified by the term lactose . " about . ” Accordingly , unless otherwise indicated , implicitly Feed conversion rate : A measure of the efficiency of an or explicitly , the numerical parameters set forth are approxi- 60 animal to convert feed mass into increased body mass ; also mations that may depend on the desired properties sought known in the art as feed conversion ratio ( which is expressed and / or limits of detection under standard test conditions / herein as a dimensionless number ) . methods. When directly and explicitly distinguishing Feedstuff: Anything that may be consumed by an animal. embodiments from discussed prior art , the embodiment The term " feedstuff " includes , but is not limited to , solid and numbers are not approximates unless the word “ about" is 65 liquid animal feeds ( e . g . , a feed ration ) , supplements ( e . g . , a recited . Furthermore , not all alternatives recited herein are mineral supplement ) , water, and feed additive carriers ( e . g ., equivalents . molasses ) . US 10 , 413 , 581 B2 12 Saponin : A class of chemical compounds , one of many iensis , Quillaja lanceolata , Quillaja lancifolia , Quillaja secondary metabolites found in natural sources, with molinae , Quillaja petiolaris , Quillaja poeppigii, Quillaja saponins found in particular abundance in various plant saponaria , Quillaja sellowiana , or Quillaja smegmadermos. species. More specifically , they are amphipathic glycosides In particular disclosed embodiments the Quillaja is Quillaja grouped , in terms of structure , by their composition . In 5 saponaria . certain embodiments, saponin comprises one or more hydro - A person of ordinary skill in the art will appreciate that, philic glycoside moieties combined with a lipophilic triter as used herein , a plant name may refer to the plant as a pene derivative . whole , or to any part of the plant, such as the roots , stem or Therapeutically Effective Amount or Effective Amount: A trunk , bark , leaves, flower, flower stems, or seeds or a quantity or concentration of a specified compound or com - 10 combination thereof. These plant parts may be used fresh , or position sufficient to achieve a desired effect in an animal dried , and may be whole , pulverized , mashed , comminuted , being treated for a disorder . The therapeutically effective or ground . The name may also refer to extracts from any part amount may depend at least in part on the species of animal or parts of the plant, such as chemical extracts , or extracts being treated , the size of the animal , and /or the severity of obtained by pressing , or any other methods of concentrating the disorder . or extracting oils or other extracts known to those in the art II. Compositions and Combinations or that are hereafter discovered . Plant extracts may include compounds that are saponins, triterpenoids, polyphenols , Disclosed herein are embodiments of a combination of antioxidants, resveratrol, or combinations thereof. A com Yucca or Quillaja , more typically both , with an antimicro - 20 position comprising Yucca and /or Quillaja can be used to bial, an antibiotic , an anticoccidial agent, and /or a vaccine , make embodiments of the disclosed combination . Such such as a coccidiosis vaccine . In some embodiments, the compositions can also include carriers and binding agents disclosed combination embodiments may be administered suitable to formulate the Yucca and / or Quillaja for admin prophylactically or therapeutically , to an animal to reduce istration to animals . In some embodiments , the compositions the risk of the animal from developing particular diseases, 25 are formulated for administration to mammals , avian , or such as coccidiosis , and / or to treat an animal suffering from aquaculture species . In certain independent embodiments , a disease , such as coccidiosis . In some embodiments , the the composition can be a commercially available product, disclosed combinations also can improve the feed conver - such as a composition comprising Yucca schidigera and sion rate of certain animals that are raised for human Quillaja saponaria , which is sold under the trade name consumption , such as domestic fowl and livestock . In yet 30 NUTRAFITO PLUS by Desert King International and /or additional embodiments , the combinations and composi- MAGNI- PHI by Phibro Animal Health Corporation . Such tions can be used to improve animal health generally . composition embodiments can comprise 85 % Quillaja In some embodiments, the compositions and combina - saponaria and 15 % Yucca schidigera or 90 % Quillaja tions disclosed herein can be used to significantly reduce the s aponaria and 10 % Yucca schidigera . costs associated with animal production . In particular 35 In some embodiments , the combination also comprises an embodiments , the compositions and combinations can sig - antimicrobial, an antibiotic , an anticoccidial agent, a vac nificantly reduce the costs associated with avian ( e . g ., cine , and /or combinations of such components . The combi domestic fowl) production as the compositions and combi n ation components can be administered in any order . In nations provide improvements in animal health and growth . some embodiments , an antimicrobial, an antibiotic , an anti Solely by way of example , a reduction of just one point in 40 coccidial agent, and a vaccine can be administered to the feed conversion ratio for 1 million chickens per week can animal prior to administration of Yucca , Quillaja , or a translate into a cost/ feed savings of nearly $ 750 ,000 per composition thereof. Alternatively , a vaccine can be admin year. Some embodiments of the combinations disclosed istered to an animal, followed by administration of Yucca , herein can provide reductions of 5 or more points in feed Quillaja , or a composition thereof. In such embodiments , an conversion , thus illustrating their utility and superior activ - 45 antimicrobial, an antibiotic and / or an anticoccidial agent ity . may be administered simultaneously with the Yucca , Quil Examples of Yucca that can be used in the disclosed laja , or composition thereof; or an antimicrobial, an antibi combination include, but are not limited to , Yucca aloifolia , otic , and / or an anticoccidial agent may be administered Yucca angustissima, Yucca arkansana , Yucca baccata , Yucca before or after each of the Yucca and /or Quillaja . In an baileyi, Yucca brevifolia , Yucca campestris , Yucca capensis , 50 independent embodiment, an antimicrobial, an antibiotic Yucca carnerosana , Yucca cernua , Yucca coahuilensis , and /or an anticoccidial agent need not be administered . In Yucca constricta , Yucca decipiens, Yucca declinata , Yucca yet other independent embodiment, a vaccine need not be de- smetiana , Yucca elata , Yucca endlichiana , Yucca faxoni administered . ana , Yucca filamentosa , Yucca filifera , Yucca flaccida , Yucca Suitable antimicrobials and / or antibiotics include, but are gigantean , Yucca glauca , Yucca gloriosa , Yucca grandiflora, 55 not limited to , Virginiamycin , Bacitracin MD , Zinc Bacitra Yucca harrimaniae , Yucca intermedia , Yucca jaliscensis , cin , Tylosin , Lincomycin , Flavomycin , Terramycin , Neo Yucca lacandonica , Yucca linearifolia , Yucca luminosa , Terramycin , or combinations thereof. In yet additional Yucca madrensis , Yucca mixtecana , Yucca necopina , Yucca embodiments , the antimicrobial or antibiotic can be selected neomexicana , Yucca pallida , Yucca periculosa , Yucca poto from penicillin , tetracycline , ceftiofur, florfenicol, tilmi sina , Yucca queretaroensis, Yucca reverchonii , Yucca ros - 60 cosin , enrofloxacin , and tulathromycin , procaine penicillin , trata , Yucca rupicola , Yucca schidigera , Yucca schottii, benzathine penicillin , ampicillin , amoxicillin , spectinomy Yucca sterilis, Yucca tenuistyla , Yucca thompsoniana , Yucca cin , dihydrostreptomycin , chlortetracycline , gentamicin , treculeana , Yucca utahensis , or Yucca valida . In certain sulphadimidine , trimethoprim , oxytetracycline , erythromy disclosed embodiments the Yucca component is Yucca schi- cin , norfloxacin and combinations thereof. digera . 65 Suitable anticoccidial agents include , but are not limited Examples of Quillaja that can be used in the disclosed to , ionophores and chemical anticoccidial products . Iono combination include , but are not limited to , Quillaja brasil - phores can include , but are not limited to , Monensin , Salino US 10 , 413 , 581 B2 13 14 mycin , Lasalocid , Narasin , Maduramicin , Semduramicin , approved or authorized dosage level for a particular antibi Laidlomycin , or combinations thereof. otic . In some embodiments , the amount of antibiotic or Chemical anticoccidial products can include, but are not antimicrobial used can range from greater than 0 ppm to limited to , Nicarbazin , Maxiban , Diclazuril, Toltrazuril , 100 ,000 ppm , such as 0 . 25 ppm to 5 ,000 ppm , or 0 . 5 ppm Robenidine , Stenorol , Clopidol, Decoquinate , DOT (zo - 5 to 2 ,500 ppm , or 0 .75 ppm to 2 , 000 ppm , or 1 ppm to 1 , 500 alene ), Amprolium , or combinations thereof. ppm , or 5 ppm to 1 , 000 ppm , or 10 ppm to 500 ppm , or 25 Suitable vaccines can be selected from live coccidiosis ppm to 300 ppm . In yet additional embodiments , the amount vaccines, such as COCCIVAC ( e . g . , a composition compris of antibiotic or antimicrobial used can range from greater ing live oocysts of Eimeria acervulina , Eimeria mivati, than 0 mg/ kg of body weight to 100 , 000 mg/ kg of body Eimeria maxima , Eimeria mitis, Eimeria tenella , Eimeria 10 weight, such as 0 . 5 mg/kg to 2 ,500 mg/ kg , or 1 mg/ kg to necatrix, Eimeria praecox , Eimeria brunetti, Eimeria 1, 500 mg/ kg , or 5 mg/ kg to 1, 000 mg/ kg , or 10 mg/ kg to 500 hagani, or combinations thereof) , LivaCox ( a composition mg/ kg m , or 25 mg/ kg to 300 mg/ kg , or 10 - 20 mg/ kg . comprising 300 -500 live sporulated oocysts of each attenu - In some embodiments , the amount of the antimicrobial or ated line of Eimeria acervulina , E . maxima and E . tenella in antibiotic that is included in the composition can range from a 1 % w / v aqueous solution of Chloramine B ) , ParaCox ( a 15 at least 1 g / ton of feed to 230 g /ton of feed ( or at least 1 . 1 composition comprising live sporulated oocysts derived ppm to 256 ppm ), such as at least 1 g /ton of feed to 220 g / ton from E . acervulina HP, E . brunetti HP , E . maxima CP, E . of feed ( or at least 1. 1 ppm to 243 ppm ), at least 1 g /ton of maxima MFP, E mitis HP , E . necatrix HP, E . praecox HP, E . feed to 100 g / ton of feed ( or at least 1 . 1 ppm to 110 ppm ) , tenella HP, and combinations thereof) , Hatch Pack Cocci III at least 1 g / ton of feed to 50 g /ton of feed ( or at least 1 . 1 ppm ( a composition comprising oocysts derived from Eimeria 20 to 55 ppm ), or at least 1 g /ton of feed to 10 g / ton of feed ( or acervulina , Eimeria maxima, Eimeria tenella , or combina - at least 1 . 1 ppm to 11 ppm ) . Particular antimicrobials or tions thereof) , INOVOCOX ( a composition comprising antibiotics that can be used , and dosage amounts of such oocysts derived from Eimeria acervulina , Eimeria maxima, antimicrobials and antibiotics include , but are not limited to , Eimeria tenella , and a sodium chloride solution ) , IMMU - the following : Virginiamycin in an amount ranging from 5 COX ( a composition comprising live oocysts derived from 25 g /ton of feed to 25 g /ton of feed ( or 5 ppm to 27 ppm , such Eimeria acervulina , Eimeria maxima , Eimeria necatrix , as 22 ppm ) ; Bacitracin MD in an amount ranging from 40 Eimeria tenella , and combinations thereof) , Advent, or g / ton of feed to 220 g / ton of feed ( or 44 ppm to 242 ppm , combinations thereof. or 50 ppm to 250 ppm in some other embodiments ); Zinc In yet additional embodiments , other vaccines can be Bacitracin in an amount ranging from 40 g /ton of feed to 220 utilized . For example , any vaccine suitable for use in any of 30 g / ton of feed ( or 44 ppm to 242 ppm ) ; Tylosin in an amount the animals described herein can be used in the disclosed ranging from 1 g /ton of feed to 1000 g /ton of feed ( or 1 ppm combinations and methods. In some embodiments , the vac - to 1100 ppm ) ; Lincomycin in an amount ranging from 1 cine can be selected based on the particular animal to receive g / ton of feed to 5 g / ton of feed (or 1 ppm to 6 ppm ) ; the combination . In some embodiments , the vaccine can be Flavomycin in an amount ranging from 1 g / ton of feed to 5 selected based on the particular diseases to which a particu - 35 g / ton of feed (or 1 ppm to 6 ppm ) ; or combinations thereof. lar animal is susceptible . Solely by way of example , a The amount of anticoccidial agent, as will be understood vaccine administered to a ruminant can be selected from any by a person of ordinary skill in the art ( e . g . , a veterinarian ) , vaccine suitable for preventing or treating sudden death can be selected depending on the particular anticoccidial ( e . g . , clostridial diseases , anthrax , and the like ), respiratory agent used . In some embodiments , the amount of anticoc diseases ( e . g ., infectious bovine rhinotracheitis , parainflu - 40 cidial agent used can be a therapeutically effective amount enza - 3 , bovine virus diarrhea , bovine respiratory syncytial for a particular animal species . In some embodiments , the virus, Pasteurella , Haemophilus sommus, and the like ) , amount of anticoccidial agent used can range from greater reproductive diseases ( IBR , BVD , brucellosis , vibriosis , than 0 ppm to 100 ,000 ppm , such as 0 . 25 ppm to 5 , 000 ppm , lepto , trichomoniasis, and the like) , scours ( rota and corona or 0 .5 ppm to 2 ,500 ppm , or 0 .75 ppm to 2 ,000 ppm , or 1 virus , E . coli , and the like ) , pinkeye , hepatitis E virus , 45 ppm to 1 , 500 ppm , or 5 ppm to 1 , 000 ppm , or 10 ppm to 500 porcine endogenous retrovirus , swine influenza virus , por- ppm , or 25 ppm to 300 ppm . In yet additional embodiments , cine parvovirus , and the like . In some embodiments , vac the amount of antibiotic or antimicrobial used can range cines can be selected from B ALPHA , BAR -GUARD - 99 , from greater than 0 mg/ kg of body weight to 100 , 000 mg/ kg BAR - VAC , BIOMYCIN 200 , BO -BAC - 2X , BOVIKALC , of body weight, such as 0 . 5 mg/ kg to 2 ,500 mg/ kg , or 1 CALIBER , CITADEL , CYDECTIN INJECTABLE , 50 mg/ kg to 1 , 500 mg/ kg , or 5 mg/ kg to 1 , 000 mg /kg , or 10 CYDECTIN POUR -ON , C & D ANTITOXIN , DIAQUE , mg/ kg to 500 mg/ kg m , or 25 mg/ kg to 300 mg/ kg , or 10 -20 DRY -CLOX , ENTERVENE - D , EXPRESS, EXPRESS FP , mg/ kg . HETACIN - K , LYSIGIN , OCU -GUARD MB - 1 , POLY In some embodiments , the amount of the anticoccidial FLEX , PRESPONSE , PRISM 5 , PYRAMID , PYRAMID , agent that is included in the composition can range from at PRESPONSE SQ , QUATRACON - 2X , SYNANTHIC , 55 least 1 g / ton of feed to 250 g / ton of feed ( or at least 1 ppm TODAY, TOMORROW , TRIANGLE , TRIVIB 5L , TRICH to 275 ppm ), such as at least 1 g /ton of feed to 200 g/ ton of GUARD , and the like . In yet additional embodiments , the feed ( or at least 1 ppm to 242 ppm ) , or at least 1 g / ton of feed vaccine can be selected from CIRCUMVENT PCV G2, to 150 g / ton of feed (or at least 1 ppm to 165 ppm ) , at least CIRCUMVENT PCV - M G2, MAGESTIC 7 , MAXIVAC , 1 g / ton of feed to 100 g / ton of feed ( or at least 1 ppm to 110 EXCELL 5 . 0 , PROSYSTEM RCE , PROSYSTEM ROTA , 60 ppm ), or at least 1 g / ton of feed to 50 g / ton of feed (or at least TGE /ROTA , PROSYSTEM TREC , and the like . 1 ppm to 55 ppm ) . Particular anticoccidial agents that can be The amount of antimicrobial or antibiotic used is within used , and dosage amounts of such anticoccidial agents the amounts stated below but may depend on the particular include, but are not limited to , the following :Monensin in an antimicrobial or antibiotic used as will be understood by a amount ranging from 35 g /ton of feed to 110 g / ton of feed person of ordinary skill in the art . In an independent embodi- 65 (or 38 ppm to 121 ppm ); Salinomycin in an amount ranging ment, the amount of the antibiotic or antimicrobial that is from 25 g / ton of feed to 90 g / ton of feed ( or 27 ppm to 99 used can be a therapeutically effective amount that is at an ppm ); Lasalocid in an amount ranging from 35 g / ton of feed US 10 , 413, 581 B2 15 16 to 113 g / ton of feed ( or 38 ppm to 125 ppm ) ; Narasin in an amount administered is from greater than 0 ounces to greater amount ranging from 35 g /ton of feed to 72 g / ton of feed ( or than 10 ounces per ton of feedstuff , such as from 1 ounce to 38 ppm to 79 ppm ) ; Maduramicin in amount ranging from 9 ounces, or 1 ounce to 8 ounces, or 2 ounces to 7 ounces . 2 g / ton of feed to 7 g/ ton of feed (or 2 ppm to 8 ppm ); In an independent embodiment , Yucca schidigera and Quil Semduramicin in an amount ranging from 12 g / ton of feed 5 laja saponaria can be administered together in an amount to 23 g / ton of feed ( or 13 ppm to 25 ppm ) ; Nicarbazin in an ranging from 2 ounces to 8 ounces per ton of feedstuff. amount ranging from 60 g / ton of feed to 113 g / ton of feed In some embodiments , the amount of compositions com ( or 66 ppm to 125 ppm ) ; Maxiban in an amount ranging prising Yucca , Quillaja , or a combination thereof that are from 40 g / ton of feed to 90 g / ton of feed ( or 44 ppm to 99 administered to animals can be an amount sufficient to ppm ) ; Diclazuril in an amount ranging from 0 . 5 g /ton of feed 10 promote animal health , reduce susceptibility to disease , to 10 g / ton of feed (or 0 .6 ppm to 11 ppm ) ; Toltrazuril in an and / or improve feed conversion performance in animals . amount ranging from 1 g / ton of feed to 10 g / ton of feed ( or The amount of the composition comprising Yucca , Quillaja , 1 ppm to 11 ppm ) ; Robenidine in an amount ranging from or a combination thereof that can be administered to animals 20 g / ton of feed to 60 g / ton of feed (or 22 ppm to 66 ppm ) ; can be measured based on the concentration of the compo Stenorol in an amount ranging from 1. 5 g/ ton of feed to 15 15 sition per unit of feed , such as in ppm of feed . In such g / ton of feed ( or 1 . 5 ppm to 17 ppm ) ; Clopidol in an amount embodiments , the amount of the composition comprising ranging from 90 g /ton of feed to 227 g / ton of feed ( or 99 Yucca , Quillaja , or a combination thereof can range from ppm to 250 ppm ) ; Decoquinate in an amount ranging from greater than 0 ppm to 100 ,000 ppm , such as greater than 0 18 g / ton of feed to 27 g / ton of feed (or 19 ppm to 29 ppm ) ; ppm to 5 , 000 ppm , such as 50 ppm to 3 , 000 , or 100 ppm to Zoalene in an amount ranging from 25 g /ton of feed to 113 20 2 ,500 ppm , or 200 ppm to 2 ,500 ppm , or 250 ppm to 600 g /ton of feed (or 28 ppm to 125 ppm ); Amprolium in an ppm , or 150 ppm to 600 ppm , or 200 ppm to 400 ppm , or amount ranging from 20 g/ ton of feed to 227 g /ton of feed 250 ppm to 300 ppm . ( or 22 ppm to 250 ppm ) . In some embodiments, the amount of the composition The amount of vaccine administered to the animal in comprising Yucca , Quillaja , or a combination thereof that combination with any of the components described herein 25 can be administered to animals can be measured based on can depend on the type of animal to which the vaccine is the amount of the composition per unit body weight of an administered . In some embodiments , the amount of vaccine animal, such as mg/ kg BW / day and /or g /kg BW /day , used is a therapeutically effective amount ranging from wherein “ BW ” refers to body weight. In some embodiments , greater than 0 mL / animal to 1 , 000 mL / animal, or 0 .25 the amount of the composition comprising Yucca , Quillaja , mL /animal to 500 mL /animal , or 0 . 5 mL /animal to 150 30 or a combination thereof that is administered can range from mL /animal , or 1 mL/ animal to 100 mL / animal, or 2 mL /ani greater than 0 mg/ kg BW /day to 1000 mg/ kg BW /day , such mal to 50 mL /animal , or 3 mL / animal to 25 mL / animal, or as 10 mg /kg BW / day to 500 mg/ kg BW /day , or 20 mg/ kg 5 mL / animal to 15 mL / animal. BW / day to 250 mg/ kg BW /day , or 30 mg/ kg BW /day to 200 In some embodiments the composition and /or combina - mg/ kg BW / day , or 40 mg/ kg BW /day to 100 mg/ kg Bw /day . tion further comprises a vitamin , a trace mineral, a bulking 35 In yet additional embodiments , the amount of the compo agent, a carrier , a colorant, a taste enhancer, or any combi- sition comprising Yucca , Quillaja , or a combination thereof nation thereof. In other embodiments the combination fur that can be administered to an animal can be measured based ther comprises corn , soybean meal , wheat, barley, rye , on the amount of the composition per animal per day , such canola , corn oil, limestone , salt , distillers dried grains with as mg/head /day and /or g /head /day . In some embodiments , solubles (DDGS ) , dicalcium phosphate , sodium sesquicar- 40 the amount of the composition comprising Yucca, Quillaja , bonate , methionine source , lysine source , L - threonine , cho - or a combination thereof that is administered can range from line , or any combination thereof. greater than 0 mg/ head /day to 100 g/ head /day , such as 0 .25 In some embodiments , the combination can be admixed mg/ head / day to 100 g / head /day , or 1 mg/ head /day to 75 with a feedstuff . The combination can be formulated to form g /head /day , or 10 mg/ head / day to 50 g /head / day, or 50 a homogeneous mixture with the feedstuff, such as by 45 mg/head /day to 25 g /head /day . crushing , crumbling , grinding or otherwise sizing the com - In an independent embodiment, a composition comprising bination . Alternatively , the combination may be formulated Yucca schidigera and Quillaja saponaria can be adminis as a solution , suspension , or slurry with the feedstuff , or t ered using at least 200 ppm to 5 , 000 ppm , such as 200 ppm separately and then added to the feedstuff. In embodiments to 2 , 500 ppm , 200 ppm to 500 ppm , 200 ppm to 300 ppm , where the combination comprises two or more composi- 50 225 ppm to 275 ppm , or 230 ppm to 260 ppm . An exemplary tions , the compositions may be formulated separately or embodiment of the disclosed combination comprises 200 substantially together. Any of the compositions disclosed ppm , 250 ppm , or 300 ppm of a composition comprising herein also can be admixed with the feedstuff . In some Yucca schidigera and Quillaja saponaria . embodiments , a composition and the feedstuff may be In some embodiments , the ratio of Quillaja saponaria and admixed sequentially , in any order , or substantially simul- 55 Yucca schidigera can range from 70: 30 (Quillaja saponaria : taneously. Yucca schidigera ) to 90 : 10 ( Quillaja saponaria : Yucca schi In some embodiments the amount of Yucca administered digera ). In an independent embodiment, the ratio of Quillaja to an animal can range from 0 to greater than 10 ounces per saponaria and Yucca schidigera can be 85 : 15 . ton of feedstuff, typically greater than 0 ounces up to at least 10 ounces per ton of feedstuff , such as from 1 ounce to 9 60 III. Methods of Use ounces , or 1 ounce to 8 ounces , or 1 ounce to 7 ounces . The amount of Quillaja administered to an animal can range Disclosed herein are embodiments of a method of using from 0 to greater than 10 ounces per ton of feedstuff , the compositions and combinations disclosed herein . Certain typically greater than 0 ounces up to at least 10 ounces per method embodiments can concern administering the dis ton of feedstuff , such as from 1 ounce to 9 ounces , or 1 ounce 65 closed compositions and /or combinations to an animal to to 8 ounces , or 1 ounce to 7 ounces . In certain embodiments , treat and / or prevent certain diseases, such as coccidiosis . In both Yucca and Quillaja are administered , and the combined some disclosed embodiments , administering the composi US 10 , 413 , 581 B2 17 18 tion and / or combination result in reducing negative effects health or increase milk production . In some embodiments , a associated with diseases , such as coccidiosis , in animals , composition comprising Yucca , Quillaja , or a combination such as , but not limited to , poor body weights , feed conver - thereof can be administered to a ruminant or ungulate in an sion rates , oocyst production , and /or lesion scores . In some amount ranging from greater than 0 ppm to 100 , 000 ppm , embodiments , the animal can be an animal raised for human 5 such as greater than 0 ppm to 5 , 000 ppm , such as 50 ppm to consumption or a domesticated animal . Examples of animals 3 , 000 , or 100 ppm to 2, 500 ppm , or 200 ppm to 2 , 500 ppm , that can be administered the compositions and combinations or 250 ppm to 600 ppm , or 150 ppm to 600 ppm , or 200 ppm disclosed herein include , but are not limited to , mammals , to 400 ppm , or 250 ppm to 300 ppm . In exemplary embodi such as livestock ( e . g ., feed or dairy cattle ) or pigs ; avian , ments, the amount of the composition comprising Yucca , such as domestic fowl ( e . g . , laying hens , chicken , turkey, 10 Quillaja , or a combination thereof that is administered to goose , duck , cornish game hen , quail, partridge , pheasant, certain ruminants , such as swine, ranges from 50 ppm to 600 guinea - fowl, ostrich , emu , swan , or pigeon ) ; aquaculture ppm . In yet additional embodiments , a composition com species, such as fish ( e . g . , salmon , trout, cod , halibut , prising Yucca , Quillaja , or a combination thereof can be snapper, herring , catfish , and the like ) , crustaceans ( e . g ., administered to a ruminant or ungulate in an amount ranging lobster, shrimp, prawns, crabs, krill , crayfish , barnacles, 15 from greater than 0 mg/ head /day to 100 g /head / day , such as copepods, and the like ) , or molluscs ( e . g . , abalone, conchs , 0 .25 mg/ head / day to 100 g /head / day , or 1 mg/ head /day to 75 rock snails , whelk , clams, oysters, mussels , cockles, and the g /head /day , or 10 mg/ head /day to 50 g /head / day, or 50 like ). In other embodiments , the animal can be a domestic mg/ head /day to 25 g/ head /day . animal , such as a dog , cat , fish , or rabbit. In some other In yet additional embodiments, the composition compris embodiments , the animal can be a ruminant species, such as 20 ing Yucca , Quillaja , or a combination thereof can be admin a sheep , goat, cow , deer, bison , buffalo , or llama. In yet other istered to aquaculture species . In such embodiments , the embodiments , the animal can be an ungulate , such as a methods can comprise providing the aquaculture species an horse , donkey, or pig . amount of the composition that ranges from greater than 0 In some embodiments , the method comprises administer ppm to 100 , 000 ppm , such as 100 ppm to 50 , 000 ppm , or ing a combination comprising a first composition and a 25 200 ppm to 25 ,000 ppm , or 300 ppm to 15 ,000 ppm , or 400 second composition . The first composition can comprise ppm to 5 , 000 ppm , or 500 ppm to 1 , 000 ppm . In some Yucca , Quillaja , or a combination thereof. In some embodi - exemplary embodiments , the amount ranges from 300 ppm ments , the first composition comprises Yucca schidigera , to 2 ,000 ppm , such as 300 ppm to 500 ppm . Quillaja saponaria , or a combination thereof. In some In an independent embodiment, the method can comprise embodiments , the method can comprise administering an 30 administering a composition comprising Yucca , Quillaja , or amount of a composition comprising Yucca , Quillaja , or a a combination thereof wherein the amount of the composi combination thereof to an animal in amounts ranging from tion that is administered ranges from at least 200 ppm to greater than 0 ppm to 100 , 000 ppm , such as 0 ppm to 5 ,000 5 , 000 ppm , such as 200 ppm to 2 , 500 ppm , 200 ppm to 500 ppm , or 10 ppm to 3 ,000 ppm , or 25 ppm to 4 ,000 ppm , or ppm , 200 ppm to 300 ppm , 225 ppm to 275 ppm , or 230 ppm 50 ppm to 3 ,000 , or 100 ppm to 2 ,500 ppm , or 200 ppm to 35 to 260 ppm . An exemplary embodiment of the disclosed 2 , 500 ppm , or 250 ppm to 600 ppm , or 250 ppm to 300 ppm . combination comprises 200 ppm or 250 ppm of a compo In some embodiments , the method can comprise admin - sition comprising Yucca schidigera and Quillaja saponaria . istering an amount of a composition comprising Yucca , In some embodiments , administration of a composition Quillaja , or a combination thereof ranging from greater than comprising Yucca and Quillaja , such as Yucca schidigera O mg/head / day to 100 g /head / day , such as 0 . 25 mg/ head /day 40 and Quillaja saponaria , provides a health benefit to an to 100 g /head / day, or 1 mg/ head / day to 75 g /head /day , or 10 animal compared to an animal that is not administered the mg/ head / day to 50 g / head / day, or 50 mg/ head / day to 25 composition . The composition may be administered alone, g /head /day . or in combination with an antimicrobial, an antibiotic , an In some exemplary embodiments of the disclosed meth anticoccidial agent, a vaccine , or a combination thereof, as ods , the first composition comprises Yucca schidigera , Quil - 45 disclosed herein . In some embodiments , the composition is laja saponaria and the composition is administered to avian . administered in the amounts disclosed herein . The health In such embodiments , the amount of the first composition benefit may include , but is not limited to , an anticoccidial can range from greater than 150 ppm to 5 , 000 ppm , such as effect , as determined by a reduction in the number of at least 200 ppm to 5 , 000 ppm , such as at least 200 ppm to coccidian oocysts detected in fecal samples ; a reduction in 500 ppm , or 250 ppm to 300 ppm of a composition com - 50 the number of Necrotic Enteritis lesions caused by prising Yucca schidigera , Quillaja saponaria , or a combi - Clostridium perfringens ; a reduction in the impact of field nation thereof. infections and trophozoite burden caused by Cochlosoma In some embodiments , the methods can comprise admin anatis infections ; and / or a beneficial effect on the microbi istering the compositions disclosed herein to animals other ome of the animal. The beneficial effect on the microbiome than chickens and turkeys . In some embodiments concern - 55 of the animal, such as the gut bacterial community , may ing administering a first composition comprising Yucca include , but is not limited to , a decrease in Clostridium schidigera and Quillaja saponaria to animals other than species , such as Clostridiaceae ; a decrease in cyanobacterial chickens or turkeys , the amount of the first composition that sequences ; a decrease in Enterococcus species , including is administered can range from greater than 0 ppm to Enterococcus cecorum ; a decrease in E . coli ; a decrease in 100 , 000 ppm , such as greater than 0 ppm to 5 ,000 ppm , or 60 Corynebacterium species ; a decrease in Staphylococcus 50 ppm to 3 ,000 , or 100 ppm to 2 ,500 ppm , or 200 ppm to species ; a decrease in Streptococcus species ; an increase in 2 , 500 ppm , or 250 ppm to 600 ppm , or 250 ppm to 300 ppm . Lactobacillus species, such as, Lactobacillus reuteri ; an In some embodiments , the method can comprise admin increaseincreas in segmented filamentous bacteria (Candidatus istering the compositions or combinations to ruminants or Arthromitus) ; an increase in Peptostreptococcaceae , includ ungulates. Such embodiments can comprise administering a 65 ing butyrate producing bacteria that have been shown to be disclosed composition or combination embodiment to a positively correlated with improved gut health ; or any livestock animal in an amount suitable to improve animal combination thereof. The health benefit may occur at any US 10 ,413 ,581 B2 19 20 time during the time period during which the composition is weeks . In some embodiments , the combination or compo administered . In some embodiments , the composition is sition can be fed to an animal that is raised for human administered from the day of age , and the health benefit may consumption from day of age to day of death , or from day occur at any time from the day of age , such as from the day of age to a time period prior to death . of age to day of harvest. 5 Method embodiments disclosed herein improve an ani In certain method embodiments , the second composition mal' s feed conversion rate , such as by reducing the animal' s can comprise an antimicrobial, an antibiotic , an anticoccidial feed conversion rate value, relative to animals that are fed a agent, a vaccine , or a combination thereof. In some embodi standard diet ( e . g . , a feedstuff ) . In an independent embodi ments , the second composition comprises Virginiamycin , ment , the method described herein can be used to improve an animal' s feed conversion rate relative to animals that are Salinomycin , or a combination thereof. The amount of the 10 solely fed a feedstuff in combination with amounts of a antibiotic , antimicrobial, anticoccidial agent, or vaccine in composition comprising Yucca schidigera and Quillaja the second composition can range from any of the amounts saponaria ranging from 100 ppm to 150 ppm . In some disclosed for such components provided herein . In some embodiments , the animal is an animal raised for human embodiments , the amount of the antibiotic , antimicrobial, consumption , such as a domestic fowl and /or livestock . A anticoccidial agent, or vaccine can range from greater than 15 feed conversion rate ( feed conversion ratio ) is a measure of O ppm to 500 ppm , such as 10 ppm to 100 ppm , or 10 ppm an animal' s efficiency in converting feed mass into increased to 70 ppm . In some embodiments , the amount ranges from body mass. In embodiments wherein the combination or at least 10 ppm to 30 ppm Virginiamycin and / or at least 25 composition is administered to an avian , such as a domestic ppm to 90 ppm Salinomycin , such as 20 ppm to 80 ppm , 20 fowl, an avian (e . g. , domestic fowl) exhibiting a low feed ppm to 70 ppm , 20 ppm to 60 ppm , or 20 ppm to 50 ppm . 20 conversion rate ( e . g . , at least one to less than 2 , such as Exemplary amounts in certain working embodiments greater than 1 to 1 . 8 , 1 . 7 , 1 . 6 , 1 . 5 , 1 . 4 , or lower ) is consid include, but are not limited to , 22 ppm Virginiamycin and /or ered efficient, as it requires less feed to reach a desired 50 ppm to 70 ppm , such as 66 ppm Salinomycin . weight. In some embodiments , a low feed conversion rate Method embodiments disclosed herein also can comprise for pigs can be 1 to 3 , such as 1 to 3 , or 2 to 3 . In some administering the combination comprising the first compo - 25 embodiments , a low feed conversion rate for cattle can be 5 to 8 , such as 6 to 8 , or 7 to 8 . In some embodiments the feed sition and the second composition in combination with a conversion rate of an avian , such as a domestic fowl, can be feedstuff . For example , the combination of the first compo enhanced by 0 .5 % to greater than 20 % , such as 2 % to 10 % , sition and the second composition can be administered in and in certain independent embodiments , by 3 % to 5 % . combination with an amount of feedstuff suitable for obtain Exemplary embodiments disclosed herein provide a feed ing an animal having a weight suitable for that particular 30 conversion rate enhancement of broiler meat- type chickens species. Solely by way of example , some embodiments can of 4 - 5 % . comprise administering the first composition and the second Some method embodiments disclosed herein also com composition in combination with 7 lbs to 10 lbs of a prise reducing the concentration of oocysts in feces of feedstuff to a chicken . Any suitable dosage of the combina animals , thereby reducing the incidence of coccidiosis in tion comprising the first composition , second composition , 35 such animals , by administering an embodiment of the com and the feedstuff may be used . In some embodiments , the bination and / or composition . In some embodiments , the amount of the feedstuff that is provided to the animal can be method can comprise administering a combination or com varied according to their food intake needs as growth occurs . position disclosed herein to an animal and then evaluating In some embodiments , the combination can comprise a the number of oocysts produced by the animal in compari first composition comprising Yucca schidigera and Quillaja 40 son to an animal that has not been administered the combi saponaria , a second composition comprising an antimicro - nation and / or composition . In some embodiments , the num bial agent and / or an antibiotic , and a third composition ber of oocysts can be reduced by a factor of 2 , 3 , 4 , 5 , or 6 , comprising a vaccine . A feedstuff also may be administered or by about 20 % to 80 % , such as 20 % to 70 % , 20 % to 60 % , in such embodiments . The combination of the first , second , or 20 % to 50 % . In certain vaccinated animals , such as and /or third compositions that is administered can be 45 domestic fowl, the number of oocysts can range from 10 , 000 admixed with a feedstuff prior to administration to the to 20 ,000 oocysts per gram of feces, which can be reduced animal, or the feedstuff may be administered before or after by a factor of four or 25 % . the combination of the first, second , and / or third composi tions . These embodiments are not intended to limit the order IV. Working Examples of administration , as any suitable order of administrationation cancan 3050 The subjectsu matter disclosed herein is further understood be selected . by reference to the following examples , which are intended The combination and /or composition embodiments dis- to be purely exemplary of certain working embodiments of closed herein can be administered using any suitable tech - the present disclosure . The present disclosure is not limited nique . In some embodiments , the combination and / or the in scope by the exemplified embodiments , which are composition is orally administered by actively introducing 55 intended as illustrations of single aspects of the claimed the combination into the animal' s mouth , or orally admin - invention only. Any methods that are functionally equivalent istered by allowing the bird to ingest the combination and / or are within the scope of the claimed invention . Various composition on its own . The combination and / or composi- modifications of the presently disclosed subject matter, in tion may be administered to the animal during any stage of addition to those described herein , will become apparent to its lifecycle in which they consume food . In some embodi- 60 those of ordinary skill in the art from the foregoing descrip ments, the animal is an avian , such as a domestic fowl and tion and accompanying figures . Such modifications fall the combination or composition disclosed herein is admin within the scope of the appended claims. istered after hatching ( or “ day of age ” ) , or at any stage thereafter, such as day of age to 42 days after birth , or 18 Example 1 days after birth to 35 days after birth . In some embodiments , 65 the combination or composition can be fed to 18 day -old In this example , the disclosed combination was adminis broiler chickens , and thereafter until harvest , typically at 8 tered to broiler chickens to determine doses in which the US 10 , 413 , 581 B2 21 22 disclosed combination can be administered without nega composition and no Virginiamycin ) and feeding phase for tively affecting feed intake and at what level of administra each dose over the control embodiment for each embodi tion toxicity occurs . ment. Approximately 50 broiler chickens were kept in pens (8 pens in total , with 50 birds per pen ) and fed a composition 5 TABLE 1 comprising Yucca schidigera and Quillaja saponaria (re Yucca schidigera and ferred to in Examples 1 -5 herein as “ the composition ” or the Quillaja saponaria Starter Grower Withdrawal “ Yucca schidigera and Quillaja saponaria composition ” ) at Composition (ppm ) 0 - 18 d 18 -32 d 32 -42 d Total different doses. The doses used in this particular example 150 50 28 89 included feed with 0 ppm of the composition , 125 ppm of the 200 2 94 composition , 250 ppm of the composition , 500 ppm of the 250 52 98 composition , and 2 , 500 ppm of the composition . No disease challenge was administered to the pen . Performance mea surements were conducted , food intake was assessed , and 1 Example 3 death incidence measured . The results obtained from this particular embodiment are illustrated graphically in FIGS . In this embodiment, the effects of an embodiment of the 1 - 3 . disclosed combination in broilers vaccinated for coccidiosis As illustrated in FIG . 1 , performance in the form of was determined . In this example , the combination comprised average weight and adjusted feed conversion ) was first 20 the Yucca schidigera and Quillaja saponaria composition , measured after 28 days , with doses of 250 ppm and 500 ppm an antibiotic composition , and /or a vaccine composition . providing better feed conversion than 0 ppm and/ or 125 ppm Also , the ability of the Yucca schidigera and Quillaja doses. FIG . 2 illustrates results obtained from days 28 - 42 of saponaria composition to enhance the activity of the anti the study , such results again indicating lower feed conver - biotic ( in this example, Virginiamycin ) composition and /or sion numbers for doses of 250 ppm and 500 ppm than that 25 the vaccine composition in coccidiosis - vaccinated birds was achieved from feeding the birds feed only and / or feed determined . In this embodiment, all birds were vaccinated including 125 ppm of the composition . FIG . 3 illustrates for coccidiosis with CocciVac . The Yucca schidigera and results obtained on the final day of the study (day 42 ); Quillaja saponaria composition was administered in doses similar results were obtained . Accordingly , this particular of 0 ppm , 200 ppm , and 250 ppm . Virginiamycin also was embodiment establishes that there are no adverse effects in 30 administered to the broilers in doses of 0 ppm and 22 ppm . feed intake, feed conversion or body weights in birds that Feed conversion performance , the number of oocysts per ingested up to 2500 ppm . The results also indicate that gram of feces , and lesions following coccidial challenge higher doses of the composition ( e . g . , about 200 ppm to were measured . about 500 ppm ) than that typically suggested amount in the Results from this embodiment are illustrated in FIGS . art ( i . e ., 125 or 150 ppm ) can be administered to the animal 35 11 - 19 . As illustrated in FIGS. 11 - 13 , broilers that were without adverse effects . administered the vaccine alone did not show the low feed conversion rates that broilers administered with the Yucca Example 2 schidigera and Quillaja saponaria composition and / or Vir giniamycin . FIGS. 11 - 13 also illustrate that broilers admin In this example , the live performance of male broiler 40 istered with a combination of the vaccine, the Yucca schi chickens during a standard diet program with and without an digera and Quillaja saponaria composition , and embodiment of the disclosed combination was determined . Virginiamycin exhibited the lowest feed conversion rates . In this embodiment, the combination comprised Virginia Without being limited to a particular theory of operation , it mycin and different levels of the composition , particularly is currently believed that higher levels of the Yucca schidi ppm , 150 ppm , 200 ppm , and 250 ppm , and further com - 45 gera and Quillaja saponaria composition ( e . g . , at least 200 prising Avatec 90 . A disease challenge was presented in each ppm to 500 ppm ) promotes the effect of the vaccine while pen by adding coccidial contaminated litter to the pen . Virginiamycin controls bacterial growth , thereby providing Results from this embodiment are provided in FIGS. 4 - 10 . an additive effect which results in an overall improvement in Body weight gain was measured on day 18 ( FIG . 4 ), days feed conversion efficiency . 18 -32 (FIG . 5 ) , day 32 ( FIG . 6 ) , days 32 -42 (FIG . 7 ) , and on 50 The effect of a combination of the vaccine , the Yucca day 42 ( FIG . 8 ) of feeding. FIGS . 9 and 10 illustrate results schidigera and Quillaja saponaria composition , and Vir from days 0 - 32 and days 0 - 42 , respectively. Virginiamycin giniamycin on weight gain also was determined . FIGS . was administered at two different dosage levels , 0 ppm and 14 - 16 illustrate these results . Additionally , the ability of 22 ppm . As indicated in FIGS . 4 - 10 , Virginiamycin coccidial organisms to reproduce in broilers administered a improved feed conversion rates throughout the test . In 55 combination of vaccine , the Yucca schidigera and Quillaja embodiments where only the composition was administered , saponaria composition , and Virginiamycin also was tested . there was not a significant improvement in the adjusted As indicated in FIG . 17 , the number of oocysts (which feed / gain , but it did significantly affect bird weight gain results from reproduction of the coccidial organisms) was throughout the tests . The results also establish that Virginia substantially reduced in broilers that had received the vac mycin and the composition provide an additive effect when 60 cine , the Yucca schidigera and Quillaja saponaria compo used in combination . As illustrated in FIG . 9 , the composi - sition , and Virginiamycin . FIG . 17 also illustrates that com tion improved bird weight gain when administered at 150 binations of the vaccine and the Yucca schidigera and ppm and 200 ppm and the overall bird weight gain response Quillaja saponaria composition resulted in decreased ( illustrated in FIG . 10 ) corroborated that good responses oocysts as well. were obtained using these two amounts of the composition . 65 In this embodiment, a challenge study was also conducted Table 1 , below , provides the body weight gain ( in grams to determine immune potentiation . On day 21 of this representing the growth response by dose ( using only the embodiment, five birds from each pen were removed and US 10 ,413 ,581 B2 23 24 challenged with a 3 - species coccidial challenge . The birds tiation of each test embodiment were evaluated and the were then placed in battery cages for seven days . At day 28, results are provided graphically in FIGS. 20 - 26 . the birds were killed and lesion scored . It was hypothesized As illustrated in FIGS. 20 - 23 , the adjusted feed conver that if immune potentiation occurred , then lesions scores sions of the birds were determined after 18 days , 28 days , following the challenge study would be lower in birds that 5 and 42 days , respectively . The results show an improvement were administered the Yucca schidigera and Quillaja in feed conversion rate in birds administered the Yucca saponaria composition than birds that were not adminis schidigera and Quillaja saponaria composition and Salino tered the Yucca schidigera and Quillaja saponaria compo mycin in combination . A significant point difference in feed sition and /or Virginiamycin . Surprisingly , however, lower conversion rate was seen after each time period , as illus lesions scores than those obtained with control birds ( e . g . , 10 trated in FIGS . 20 - 23 . Without being limited to a single vaccine only ) were not observed in birds that were admin istered the Yucca schidigera and Quillaja saponaria com theory of operation , it is currently believed that administer position in amounts ranging from about 200 ppm to 500 ing the composition in combination with Salinomycin ppm , alone or in combination , as illustrated in FIGS . 18 and increases the effectiveness of the Salinomycin in reducing 19 . Without being limited to a particular theory of operation , 15 the negative effects of coccidiosis ( e . g ., poorer feed conver it is currently believed that the higher lesion scores were sion rates) . The results also illustrated an additive effect obtained in birds that had been administered the Yucca between the composition and the Salinomycin . Body weight schidigera and Quillaja saponaria composition and / or Vir gain also increased in birds that were administered a com giniamycin than control birds because the birds that were bination of the composition and Salinomycin as compared to administered the Yucca schidigera and Quillaja saponaria 20 birds that did not receive the combination ( e . g . , birds admin composition and / or Virginiamycin experienced lower levels istered feed only , birds administered the composition only , of coccidia exposure prior to extraction from the pens . That and birds administered Salinomycin only ) . These results are is , birds administered the Yucca schidigera and Quillaja clearly illustrated in FIGS . 24 - 26 . saponaria composition at amounts of about 200 ppm to The combination of the composition and Salinomycin about 500 ppm and / or Virginiamycin exhibited better anti- 25 also reduced the number of oocysts per gram of feces in coccidial capabilities than birds that were not administered broilers , as indicated in FIG . 27 . A challenge study was also the Yucca schidigera and Quillaja saponaria composition conducted to evaluate the potential for immune potentiation . and / or Virginiamycin . The non -control birds therefore did Similar to the challenge study described in Example 3 , 5 not develop as much immunity to coccidia while in the pen birds were removed from each pen after 21 days . These birds as the control birds who were not administered the combi- 30 were challenged with a three - species coccidial challenge and nation and therefore were more susceptible to coccidia and then placed in batter cages for seven days . On day 28 , the better able to develop more immunity while in the pen . The birds were killed and lesion scored . This challenge study control birds therefore exhibited lower lesions scores once indicated independent anticoccidial effects of the composi extracted from the pens as they had already developed tion and Salinomycin as both increased the susceptibility of immunity to the coccidial challenge. The anticoccidial 35 broilers to coccidial challenge between days 21 and 28 . effects of the Yucca schidigera and Quillaja saponaria composition in amounts ranging from about 200 ppm to Example 5 about 500 ppm , alone or in combination with Virginiamycin , are therefore corroborated with the data illustrated in FIGS . In this particular embodiment, the effects of the compo 18 and 19 , as higher lesion scores are indicative of better 40 sition and Salinomycin , independently , were evaluated . coccidiosis control ( i. e ., less immunity ) . Results from these Lower amounts of the composition were tested , including lesion scoring examples are provided in FIGS. 18 and 19 . the amount that is typically used by those in the art (i . e ., 125 Based on this example , it was determined that the Yucca ppm ) . Salinomycin treatments used 44 ppm or 66 ppm schidigera and Quillaja saponaria composition , particularly Salinomycin . Non - infected birds that received no medica at amounts of about 200 ppm to about 500 ppm , exerts clear 45 tion were used as a control ( entry 1 of Table 2 , below ) . Also , anticoccidial effects in vaccinated broilers . There was an some birds were administered 66 ppm of Salinomycin , but approximate 4 - to 5 - fold reduction in fecal oocyst count where not infected ( entry 7 of Table 2 , below ) . The remain during the first 28 days in birds administered a combination ing birds were infected with 200 ,000 oocysts of field isolate of a vaccine and the Yucca schidigera and Quillaja of E . acervulina , which is a species of Eimeria that causes saponaria composition . Also , the anticoccidial effects of the 50 coccidiosis in poultry , particularly old poultry , and subjected Yucca schidigera and Quillaja saponaria composition was to the treatments described below in entries 2 - 6 of Table 2 . supported by the challenge study disclosed above, which As indicated by the data provided in Table 2 , no significant clearly showed higher susceptibility to coccidial challenge differences in body weights and /or adjusted feed conversion in birds that were not administered the Yucca schidigera and were observed at the lower levels of the Yucca schidigera Quillaja saponaria composition . 55 and Quillaja saponaria composition (abbreviated as “ YQ composition " in Table 2 ) used in these tested embodiments . Example 4 TABLE 2 In this particular embodiment, the compatibility of the Yucca schidigera and Quillaja saponaria composition with 60 E . acervulina Feed Adj . Fd . Avg. Wt. Lesion Salinomycin was evaluated . The treatments included Treatment Consum . Conv. Gain Score OPG * * embodiments where no feed additive was provided ( e . g ., NM * Noninfect 2 . 796 a 1 . 791 b 0 . 260 a 0 .0 d none of the composition added ) , where 250 ppm of the NM , Infect 2 .531 bc 2 . 125 a 0 . 203 c 2 . 1 a 26780 YQ composition 2 .441 c 2 . 125 a 0 .194 c 1. 7 bc 24645 composition was provided , where 66 ppm of Salinomycin 100 ppm was provided , and embodiments where 250 ppm of the 65 YQ composition 2 .436 C 2 .136 a 0 .191 C 2 . 0 ab 22411 composition and 66 ppm of Salinomycin were provided in 125 ppm combination . The anticoccidial effects and immune poten US 10 , 413 ,581 B2 25 26 TABLE 2 - continued Accordingly , the results provided in this example estab E . acervulina Feed Adj. Fd . Avg . Wt. Lesion lish that amounts of the Yucca schidigera and Quillaja Treatment Consum . Conv. Gain Score OPG * * saponaria composition ranging from 100 ppm to 150 ppm YQ composition 2 .490 € 2 . 186 a 0. 192 c 2 . 3 a 36301 are not as effective in improving feed conversion rates of 150 ppm animals as are amounts of the Yucca schidigera and Quillaja Sal 44 ppm 2 . 804 a 1 . 946 b 0 . 241 ab 1 . 3 c 2734 saponaria composition that range from about 200 ppm to Sal 66 ppm 2 .692 ab 1. 948 b 0 . 231 b 1 .4 C 217 about 500 ppm . The results also reflect that amounts of the * NM = non -medicated treatments Yucca schidigera and Quillaja saponaria composition rang * * OPG = oocysts per gram of fecal material 10 ing from 100 ppm to 150 ppm do not have the same Similar protocols were used to determine the effects of anticoccidial activity as those embodiments wherein about lower amounts of NFP ( e .g ., 100 ppm , 125 ppm , and 150 200 ppm to about 500 ppm of the Yucca schidigera and ppm ) on birds infected with E . maxima, a common form of Quillaja saponaria composition is used . Eimeria found in commercial broilers . Infected birds were infected with 37, 500 oocysts of field isolate of E . maxima. The infected birds were subjected to the treatments General Procedures for Examples 6 -8 described below in entries 2 - 6 of Table 3 . As indicated by the data provided in Table 3 , no significant differences in body In the embodiments described below in Examples 6 -8 , the weights and /or adjusted feed conversion were observed at 20 following conditions andand memethods were utilized . The test the lower levels of the Yucca schidigera and Quillaja house was divided into pens of equal size , arranged along a saponaria composition ( abbreviated as “ YQ composition ” central aisle . Subtracting out for equipment, the initial bird in Table 3 ) used in these tested embodiments . density was ~ 0 . 84 square ft /bird . Each pen had 5 feet high side walls with bottom 11/ 2 feet being of solid wood to TABLE 3 25 prevent bird migration . All flooring of each pen had approxi E . maxima Feed Adj. Fd . Avg . Wt. Lesion mately 4 inches of built -up litter . Treatment Consum . Conv. Gain Score OPG The temperature of the building was monitored . Environ NM , Noninfect 2 . 796 a 1 .791 c 0 . 260 a 0 . 0 e mental conditions during the trial ( temperature ) were appro NM , Infect 2 . 674 ab 2 . 225 a 0 . 201 c 1 . 9 ab 1884 YQ composition 2. 638 bc 2 . 191 a 0 . 202 c 1 . 8 ab 11072 2 priate (optimum ) to the age of the animals Illumination was 100 ppm provided by fluorescent bulbs placed above the pens . The YQ composition 2. 534 c 2. 216 a 0 . 191 c 1 .6 bc 335 lighting scheme was 24 hours of light per day. 125 ppm YQ composition 2 .611 bc 2 .258 a 0 . 194 c 2 .0 a 1100 The diets were provided ad libitum in one tube- type 150 ppm feeder per pen . From day 1 until day 7 , feed will also be Sal 44 ppm 2 .718 ab 2 .021 b 0 .225 b 1 . 3 cd 4435 35. Gunnlied on a tray placed directly on the litter of each mon Sal 66 ppm 2 .647 bc 1 . 960 b 0 . 230 b 1 . 2 d 167 35 supplied on a tray placed directly on the litter of each pen . Standard floor pen management practices were used * NM = non -medicated treatments throughout the experiment. Animals and housing facilities * * OPG = oocysts per gram of fecal material were inspected twice daily , observing and recording the In another test embodiment, the effects of lower amounts 10 general health status, constant feed and water supply as well of NFP ( e . g ., 100 ppm , 125 ppm , and 150 ppm ) on birds as temperature , removing all dead birds, and recognizing infected with E . tenella , a species of Eimeria that causes unexpected events . hemorrhagic cecal coccidiosis in poultry , particularly young poultry . Infected birds were infected with 100 , 000 oocystsoung of All feeds were fed as crumbles /pellets . Quantities of all field isolate of E . tenella . The infected birds were subjected basal feed and test articles used to prepare treatment batches to the treatments described below in entries 2 - 6 of Table 4 *. 45 were documented . Each batch of feed was mixed and bagged As indicated by the data provided in Table 4 , no significant separatelyse . Each bag was identified with the study number , differences in body weights and / or adjusted feed conversion date of mix , type of feed , and the correct treatment number . were observed at the lower levels of the Yucca schidigera Complete records of feed mixing , and test article inventories and Quillaja saponaria composition ( abbreviated as “ YQ were maintained . A sample from the beginning , middle , and composition ” in Table 4 ) used in these tested embodiments . 30 end of each treatment feed were mixed to form a composite sample . This sample of each treatment was retained until TABLE 4 study end . All feed was weighed by pen . Starter feed was fed from Day 0 to 18 . On Day 18 , non - consumed starter was E . tenlla Feed Adj. Fd . Avg . Wt. Lesion OPG ss weighed and discarded . Grower feed was issued and fed Treatment Consum . Conv. Gain Score until Day 28 . On Day 28 , non - consumed grower was NM , Noninfect 2 . 796 a 1 . 791 c 0 . 260 a 0 . 0 d 0 NM , Infect 2 . 770 a 2 .012 a 0 . 236 b 1 . 9 a 1984 weighed and discarded . Finisher feed was issued and fed YQ composition 2 . 692 a 2 .017 a 0 . 226 b 1 . 3 b 617 until Day 42 . On Day 42 , non - consumed finisher was 100 ppm weighed and discarded . YQ composition 2 .757 a 1 .999 a 0. 231 b 1. 5 b 11589 125 ppm 60 Day of hatch male chicks were obtained from Cobb YQ composition 2 .723 a 1 . 892 b 0 . 240 ab 1 . 6 ab 2267 Vantress hatchery , Cleveland , Ga. The strain was Cobb 500 . 150 ppm Breeder flock was recorded . 1760 chicks were allocated to Sal 44 ppm 2 .787 a 1 . 929 ab 0 .242 ab 0 . 8 c 800 the study. At the hatchery, the birds received routine vacci Sal 66 ppm 2 . 671 a 1 . 863 bc 0 . 245 ab 0 .6c 150 nations. The birds were sexed at the hatchery . In Example 7 , * NM = non -medicated treatments 65 all chicks were spray vaccinated with conventional doses of * * OPG = oocysts per gram of fecal material Coccivac - B . Only healthy appearing chicks were used in the study . In examples 6 and 7 , fifty - five males were allocated US 10 , 413 , 581 B2 27 28 to each treatment pen by blocks. In example 8 , fifty -two TABLE 5 - continued males were allocated to each treatment pen by blocks . No birds were replaced during the course of the study . Number Feed Adj. Avg. Wt and disposition of all birds not used for allocation were Treatments Intake FCR Gain documented . Bird weights (kg ) by pen were recorded at 5 3 . Sal 66 ppm + Composition 250 ppm 85 .36a 1 . 701a 0 .920a study initiation , Day 18 , 28 , and termination (Day 42 ) . D 29 -42 On Days 18 , 28 , and 35 , three birds per pen were 4 . Sal 66 ppm + Composition 250 ppm 86 .28a 1 . 676ab 0 . 941a sacrificed and coccidial lesion scored for degree of E . D 19 - 42 acervulina , E . maxima and E . tenella infection ( Examples 6 Day 42 and 7 ) . The system of Johnson and Reid ( 1970 ) wherein 0 is 10 normal and 1 , 2 , 3 , or 4 indicate increasing severity of 1. Sal 66 ppm + Composition 250 ppm 212 . 19a 1 .807 2 . 412a infection were used for lesion scoring . In Example 8 , three D 0 - 42 birds per pen were sacrificed on days and 28 and coccidial 2 . Sal 66 ppm + Composition 250 ppm 208. 87a 1 . 837bc2 . 376a lesion scored for degree of E . acervulina , E . maxima and E . D 0 - 28 tenella infection . The system of Johnson and Reid ( 1970 ) 15 3 . Sal 66 ppm + Composition 250 ppm 206 .71a 1 . 887a 2 . 295a wherein 0 is normal and 1, 2 , 3 , or 4 indicate increasing D 29 -42 severity of infection were used for lesion scoring . 4 . Sal 66 ppm + Composition 250 ppm 205. 66a 1. 859ab 2. 295a On Days 18 and 28 fresh fecal samples were collected D 19 - 42 from each pen (Examples 6 and 7 ) . On Days 18 and 28 , fresh " D " = days ; letters " , " " b , " and " c " are used to indicate break points based on statistical analysis and thereby provide an indication of statistically significant differences between These representative samples were tested to determine the observed values . degree of oocysts shedding /cycling . Oocysts per gram were determined for each sample . TABLE 6

Example 6 25 Feed Adj. Avg. Wt Treatments Intake FCR Gain In this particular example , compositions were adminis Day 18 tered for different time periods during the life span of birds to determine preferred administration time periods for 1. Sal 66 ppm + Composition 250 ppm 33 . 196 1 .445a 0 . 377a D 0 - 42 improved performance . Also studied were the control of 30 2 . Sal 66 ppm + Composition 250 ppm 33 .23b 1. 445a 0 .377a field strains less sensitive to ionophore medication and the D 0 - 28 performance of composition embodiments alone or in com 3 . Sal 66 ppm + Composition 250 ppm 35 . 46a 1. 474a 0 . 394a bination with Salinomycin fed to broilers . D 29 - 42 Birds were administered a diet comprising 250 mg of a 4 . Sal 66 ppm + Composition 250 ppm 35 .09ab 1 .4832 0 . 391a composition embodiment comprising 90 % Quillaja 35 DayD 19 -2842 saponaria and 10 % Yucca schidigera in combination with 66 ppm of Salinomycin for different time periods. In some 1 . Sal 66 ppm + Composition 250 ppm 85 .06a 1 . 6526 0 .944a D 0 - 42 embodiments , the composition embodiment was fed to the 2 . Sal 66 ppm + Composition 250 ppm 85 . 59a 1 .6496 0 .948a birds for the entire period between birth and death ( typically D 0 - 28 days 0 to 42 , referred to as a “ full program ” ) or during 40 3. Sal 66 ppm + Composition 250 ppm 85 . 36a 1. 701a 0 .920a D 29 -42 intermediate time periods during the birds ' life spans, such 4 . Sal 66 ppm + Composition 250 ppm 86 . 28a 1 .676ab 0 . 941a as from days 0 to 28 ( referred to as a “ starter / grower D 19 - 42 program ” ) , from days 29 -42 ( referred to as a “ finisher Day 42 program ” ) , or from days 19 -42 ( referred to as a “ grower / finisher program ” ) . The birds were exposed to a coccidial 45 1. Sal 66 ppm + Composition 250 ppm 212. 19a 1. 807 2 . 412a D 0 - 42 challenge from day of age ( e . g ., day 0 ) . Numerical results 2 . Sal 66 ppm + Composition 250 ppm 208. 87a 1 .837bc2 .376a are provided by Tables 5 - 7 and also are presented graphi D 0 - 28 cally by FIGS. 28 - 37 . 3 . Sal 66 ppm + Composition 250 ppm 206. 71a 1. 887a 2 . 295a D 29 - 42 4 . Sal 66 ppm + Composition 250 ppm 205. 66a 1. 859ab 2 . 295a TABLE 5 D 19 - 42 Feed Adj. Avg. Wt " D " = days; letters " ," " , " and " c " are used to indicate break points based on statistical Treatments Intake FCR Gain analysis and thereby provide an indication of statistically significant differences between observed values . Day 18 1 . Sal 66 ppm + Composition 250 ppm 33. 19b 1 .445a 0 .377a 55 TABLE 7 D 0 -42 2. Sal 66 ppm + Composition 250 ppm 33 .23b 1 .445a 0 . 377a Treatments E . A . E . M . E . T . AVG D 0 - 28 3. Sal 66 ppm + Composition 250 ppm 35. 46a 1. 474a 0 . 394a Lesions Day 18 D 29 - 42 4 . Sal 66 ppm + Composition 250 ppm 35 .09ab 1 .483a 0 . 391a V 1. Sal 66 ppm + Composition 250 ppm 2 .4a 1. 5a 0 . 2ab 1 .4a D 19 - 42 D 0 - 42 Day 28 2. Sal 66 ppm + Composition 250 ppm 2. 3a 1. 0a 0. 4a 1. 2a D 0 - 28 1 . Sal 66 ppm + Composition 250 ppm 85 . 062 1 .652b 0 .944a 3. Sal 66 ppm + Composition 250 ppm D 0 - 42 D 29 - 42 2. 2a 1. 4a 0. 26 1. 3a 2 . Sal 66 ppm + Composition 250 ppm 85 .59a 1 .649b 0 .948a 65 4 . Sal 66 ppm + Composition 250 ppm 2 .4a 1. 3a 0 . 3ab 1 .3a D 0 - 28 D 19 - 42 US 10 , 413 ,581 B2 29 30 TABLE 7 - continued tion with a component capable of reducing the adverse effects of coccidial infection ( e .g ., a component having Treatments E . A . E . M . E . T. AVG activity against coccidia , such as Salinomycin ). With refer Lesions Day 28 ence to FIG . 32 , improved feed conversion rates are even more pronounced at day 42 as can be seen by comparing bar 1. Sal 66 ppm + Composition 250 ppm 1. 22 0 .21 0 .0 0 .4a D 0 - 42 3200 ( days 0 - 42 ) and bar 3202 ( days 0 - 28 ) . The data 2 . Sal 66 ppm + Composition 250 ppm 1 . 1a 0. 1a 0 .0a 0 .4a provided by this example illustrate that embodiments of the D 0 - 28 composition can enhance the activity of Salinomycin , and 3 . Sal 66 ppm + Composition 250 ppm 1. 4a 0 . 2a 0 .02 0 . 5a therefore can be effective with other antimicrobials , antibi 4D . 29Sal - 42 66 ppm + Composition 250 ppm 1. 42 0 .01 0 .01 0. 5a otics, and / or anticoccidial agents . D 19 - 42 The data also indicate that significant reductions in oocyst Lesions Day 35 production were observed when the birds were fed the 1 . Sal 66 ppm + Composition 250 ppm 0 . 3a 0 .32 0 . 22 0 .3a composition as compared to birds that did not receive any of D 0 -42 2 . Sal 66 ppm + Composition 250 ppm 0 . 3a 0 .22 0 .0a 0 . 2a 15 the composition ( see FIG . 28 ) . Furthermore , birds receiving D 0 - 28 a full program of the composition exhibited significant 3 . Sal 66 ppm + Composition 250 ppm 0 . 1a 0 . 22 0 .3a 0 .2a decreases in oocyst production as indicated by FIG . 29 and D 29 - 42 Table 7 . Additionally , the composition also did not exhibit 4 . Sal 66 ppm + Composition 250 ppm 0 .19 0. 22 0 .1a 0 . 1a any deleterious effects on body weight gain of the birds as D 19 -42 20 evidenced by FIGS . 34 - 37 . " D " = days; " E . A .” = E . acervulina ; " E .M .” = E . maxima; " E . T. ” = E . tenella ; letters “ a, " " b , " and " c " are used to indicate break points based on statistical analysis and thereby provide an indication of statistically significant differences between observed values . Example 7 TABLE 8 25 In this embodiment, the effects of a composition embodi Treatments E . A . E . M . E . T . Total ment in different feeds and as a complete program were evaluated in combination with the use of a coccidiosis Oocysts per gram Day 18 vaccine. The coccidiosis vaccine was administered to the 1. Sal 66 ppm + Composition 49926 1374bc 5286 6893bc birds at hatching in this example ; however , the vaccine can 250 ppm D 0 - 42 30 be administered at other times during a bird ' s life cycle and 2 . Sal 66 ppm + Composition 3400b 16160 352ab 5368c 250 ppm D 0 - 28 even in combination with the composition . The birds in this 3 . Sal 66 ppm + Composition 7471a 2705a 1072a 11248a embodiment were raised for a 42 day growth period . A 250 ppm D 29 - 42 control group of birds was used , wherein the birds were 4 . Sal 66 ppm + Composition 5394ab 2931ab 938a 9263ab vaccinated but were not fed the composition . Other groups 250 ppm D 19 -42 35 Oocysts per gram Day 28 included groups of birds fed 250 mg of a composition embodiment from day 0 to day 28 ( starter/ grower program ), 1 . Sal 66 ppm + Composition 2789ab 209ab 402b 3400b 250 ppm D 0 - 42 from day 29 to day 42 ( finisher program ) , and from day 0 to 2 . Sal 66 ppm + Composition 2295b 235b 302b 28316 day 42 ( full program ). Data from the embodiments 250 ppm D 0 - 28 40 described in this example are provided below in Tables 9 - 11 3 . Sal 66 ppm + Composition 4255a 930a 796a 5980a 250 ppm D 29 - 42 and also are illustrated graphically in FIGS. 38 - 45 . 4 . Sal 66 ppm + Composition 4020a 829ab 586a 5435a 250 ppm D 19 -42 TABLE 9 “ D ” = days ; " E . A . ” = E . acervulina ; " E . M . ” = E . maxima; " E . T . ” = E . tenella ; letters " a ," “ b , " and " c " are used to indicate break points based on statistical analysis and thereby 45 Feed Adj. Wt. provide an indication of statistically significant differences between observed values . Intake FCR Gain Mortality The data provided by Tables 5 - 8 indicate that the com Day 18 positions and combinations disclosed herein are capable of providing significant and beneficial reductions in adjusted 1 . No Additive 34 .69ab 1 . 473a 0 . 383a 50 2 . Composition D 0 - 28 33 . 82ab 1 . 408ab 0 . 393a feed conversion rates, thus illustrating the benefits of that the 3 . Composition D 28 -42 35 .66a 1 . 470a 0 . 397 compositions and combinations (e . g. , compositions and anti 4 . Composition D 0 - 42 33 . 28b 1 . 400b 0 . 391a biotics, antimicrobials , and /or anticoccidials ) can have on Day 28 animal health and productivity . In some embodiments , a significant difference (e . g ., a reduction of 2 % or higher ) in ss 1. No Additive 85 .59ab 1. 611a 0 . 977a 2 . Composition D 0 -28 81. 096 1 . 564a 0 . 976a the feed conversion rates of birds administered the compo 3 . Composition D 28 -42 86 . 30a 1 .615a 0 .975a sition for a full program was observed (see FIGS. 30 - 33 ) . In 4 . Composition D 0 -42 81 .77ab 1. 571a 0 . 986a some embodiments , using a full program of a composition / Day 42 combination ( e. g. , a composition and Salinomycin ) resulted in a 5 point difference in feed conversion . See , for example , 60 1. No Additive 191. 42a 1 .818a 2 . 186a 8 . 2a FIGS. 31 and 32 . With reference to FIG . 31, a comparison 2 . Composition D 0 -28 182. 99a 1 . 772b 2 . 223a 10 .9a of the results represented by bar 3100 (representing embodi 3. Composition D 28 - 42 190 . 18a 1 .763b 2 .243a 7 . 6a ments where no composition had been administered at the 4 . Composition D 0 -42 180 . 86a 1 . 737c 2 . 239a 10 .6a time of measurement ) with bar 3102 (representing a full " D " = days ; letters " a , " " b ," and " c " are used to indicate break points based on statistical S er analysis and thereby provide an indication of statistically significant differences between program ) corroborates that feed conversion rates can be observed values . significantly improved using the composition in combina US 10 , 413 ,581 B2 31 32 TABLE 10 from this example further illustrate that the disclosed com positions and combinations are effective to better control Treatment E. A . E .T . E. M . Total coccidia that are partially resistant to ionophores. Day 21 OPG TABLE 12 1 . No Additive 687a 335a 402a 1424a 2 . Composition D 0 -28 109b 75a 151ab 335b Feed Adj. Wt. 3 . Composition D 28 - 42 419ab 268a 260ab 946ab Intake FCR Gain Mortality 4 . Composition D 0 -42 142b 126a 67b 335b Day 28 OPG Day 18 1 . No Additive 7596a 7270a 3928a 18794a 1 . No Feed Additive 25 . 29a 1 .456a 0 .294a 2 . Composition D 0 - 28 4023a 4447a 1625a 10095b 2. Composition 250 ppm 25 .02a 1. 358bc0 . 313a 3 . Composition D 28 -42 5712a 6214a 3216a 15142ab 3 . Salinomycin (SAL ) 66 ppm 24 .76a 1 .420ab 0 .294a 4 . Composition D 0 - 42 3576a 5151a 1759a 10486b 4 . Composition 250 ppm + 25 .42a 1 . 3210 0 . 328a “ D ” = days; " E . A . " = E . acervulina ; " E . M . ” = E . maxima ; " E . T . ” = E . tenella ; letters " a , " SAL 66 ppm “ ." and " c " are used to indicate break points based on statistical analysis and thereby 1 Day 28 provide an indication of statistically significant differences between observed values . 1 . No Feed Additive 72 . 26a 1 .712a 0 . 792b 2 . Composition 250 ppm 74 .06a 1 .641b 0 . 855a TABLE 11 3 . Salinomycin (SAL ) 66 ppm 74. 09a 1 .619b 0 . 875a 4 . Composition 250 ppm + 74 . 81a 1 . 5660 0 . 909a Treatment E . A . E . M . E . T . Total 20 SAL 66 ppm Day 21 Lesion Scores Day 42 177. 32a 1 . 843a 2 . 0096 3 . 8ab 1 . No Additive 0 .7a 0 . 2a 0 .4a 0 .4a 1 . No Feed Additive 2 . Composition D 0 - 28 0 .8a 0 . 3a 0 . 1a 0 . 4a 2 . Composition 250 ppm 180 . 19a 1 .796b 2 . 108a 4 . 9ab 3 . Composition D 28 -42 0 .6a 0 . 3a 0 . 3a 0 . 4a 3 . Salinomycin (SAL ) 66 ppm 175. 68a 1 .773bc 2 . 114a 6 . 5a 4 . Composition D 0 -42 0 . 8a 0 .4a 0 . 3a 0 . 5a 25 4 . Composition 250 ppm + 178 .18a 1 .7470 2. 141a 3 . 5b Day 28 Lesion Scores SAL 66 ppm 1 . No Additive 0 . 3a 0 . 1a 0 .0a 0 . 1a 2 . Composition D 0 -28 0 . 3a 0 . 3a 0 . 0a 0 . 2a 3 . Composition D 28 -42 0 . 4a 0 . 2a 0 . 0a 0 . 2a TABLE 13 4 . Composition D 0 -42 0 . 4a 0 . 2a 0 . 0a 0 . 2a 30 Day 35 Lesion Scores Treatment E . A . E . M . E . T . Total 1 . No Additive 0 .6a 0 .4a 0 . 2a 0 .4a Day 18 Lesion Scores 2 . Composition D 0 - 28 0 . 4a 0 . 3a 0 .0a 0 .3a 3 . Composition D 28 -42 0 .6a 0 . 4a 0 . 1a 0 . 3a 1 . No Feed Additive 1 .5a 1 . 1a 1 . 0a 1 . 2a 4 . Composition D 0 - 42 0 .5a 0 .3a 0 .22 0 . 3a 35 2 . Composition 250 ppm 1 .5a 0 .8a 0 .46 0 . 9b 3 . Salinomycin (SAL ) 66 ppm 1 . 3a 0 .7a 0 .56 0 .8b “ D ” = days; " E . A . " = E . acervulina ; " E . M . ” = E . maxima ; " E . T . ” = E . tenella ; letters " a , " " b , " and " c " are used to indicate break points based on statistical analysis and thereby 4 . Composition 250 ppm + SAL 66 ppm 1 .7a 0 .92 0 .26 0 .9b provide an indication of statistically significant differences between observed values . Day 28 Lesion Scores 1 . No Feed Additive 1. 5a 1. 0a 0 . 8a 1. la 40 2 . Composition 250 ppm 0 . 86 0 .56 0 . 26 0 . 5b Example 8 3 . Salinomycin (SAL ) 66 ppm 1 .2ab 0 .56 0 . 16 0 .6b In this example , the ability of exemplary compositions to 4 . Composition 250 ppm + SAL 66 ppm 1 .06 0 . 3b 0 . 36 0 .6b " E . A . " = E . acervulina ; " E . M . ” = E . maxima; " E . T .” = E . tenella ; letters " , " " b , " and " c "? improve bird performance under challenge conditions was are used to indicate break points based on statistical analysis and thereby provide an determined . In some embodiments , an exemplary composi indication of statistically significant differences between observed values . tion was administered alone and in other embodiments , it was administered in combination with Salinomycin . In some TABLE 14 embodiments , the birds were not fed any additives ( that is , neither the composition nor Salinomycin ) and in other Treatment E . A . E . M . E . T . Total embodiments the birds were solely fed Salinomycin . The 50 Day 21 OPG birds used in this example were exposed to ionophore 1 . No Feed Additive 8191a 3719a 6332a 18241a tolerant coccidia in the litter of all pens, beginning from day 2 . Composition 250 ppm 5025b 2864ab 3819b 11708b of age . At day 18 , Salinomycin alone did not improve 3 . Salinomycin (SAL ) 66 ppm 2915bc 1910bc5528a 10352b performance . Both treatments with the composition ( com - 4 . Composition 250 ppm + SAL 15080 5530 37195 5779c position alone and composition and Salinomycin ) , however, 55 66 ppm exhibited statistically significant improvements in adjusted Day 28 OPG feed conversion rates , thus indicating that the composition , 1. No Feed Additive 6181a 2261a 5477a 13919a alone or in combination with Salinomycin , can control 2 . Composition 250 ppm 5025b 1457ab 3467a 9950b coccidia and improve performance . In yet some embodi 3 . Salinomycin (SAL ) 66 ppm 3819b9 55b 3065ab 7839b ments , the combination of the composition and Salinomycin 60 4 . Composition 250 ppm + SAL 15580 7046 21616 44220 exhibited performance improvements at later stages ( e . g ., 66 ppm after 28 days , even up to 42 days ), indicating a synergistic " E . A . " = E . acervulina ; " E . M . ” = E . maxima; " E . T. ” = E . tenella ; letters " , " " b , " and " c "! are used to indicate break points based on statistical analysis and thereby provide an indication of statistically significant differences between observed values. oocyst data obtained from this example further corroborates the effectiveness of the composition and the combination of 65 The information provided by Tables 12 - 14 indicate , in the composition and Salinomycin , as statistically significant some embodiments , that the disclosed compositions can be reductions in oocyst production were observed . The results used in combination with an antibiotic , antimicrobial, and /or US 10 , 413 , 581 B2 33 34 anticoccidial agent to improve performance even in animals TABLE 16 -continued that have developed ionophore resistance . Treatments E . G . E . M . E . A . Total Example 9 4 . 750 ppm Composition D 0 -42 267a 1391a 534a 2192a 5 5 . 1000 ppm Composition D 0 -42 334a 1039a 534a 1906a " D " = days ; " E . G . ” = E . gallopavonis ; " E . M . ” = E . meleagrimitis ; " E . A . " = E . adenoeides; In this example , the effect of an exemplary composition letters " , " " b , " and " c " are used to indicate break points based on statistical analysis and comprising Quillaja saponaria and Yucca schidigera when thereby provide an indication of statistically significant differences between observed fed to turkey hens was determined . In some embodiments , values . the composition was a commercial product sold under the 10 trade name MAGNI- PHI by Phibro Animal Health Corpo Example 10 ration . The study comprised 1575 turkeys split into seven blocks of five pens where each pen comprising 45 turkeys . In this examples the effect of a composition comprising The study was conducted from day to day 42 . The five Quillaja saponaria and Yucca schidigera in combination treatments protocols were 0 ppmm , 250 ppmppm , 500 ppm , 750175015: with Monensin was determined . In some embodiments , the ppm , and 1000 ppm . composition was a commercial product sold under the trade On Days 14 , 21 , and 28 fresh fecal samples were collected name MAGNI- PHI by Phibro Animal Health Corporation . from each pen . These representative samples were tested to Four treatment regimens were used : a control with no determine the degree of coccidia oocysts per gram of litter , 20 medication ; 250 ppm of the composition ; 68 ppm Monensin ; by determining oocysts shedding / cycling . Oocysts per gram 20 and 250 ppm composition in combination with 68 ppm were determined for each sample . Tables 15 and 16 provide Monensin . the results . With respect to Table 16 , E . G . is E . gallopavonis , On Days 14 , 21, and 28 fresh fecal samples were collected E . M . is E . meleagrimitis , and E . A . is E . adenoeides . As can from each pen . These representative samples were tested to be seen in Table 16 , the number of oocysts detected 25 determine the degree of coccidia oocysts per gram of litter , decreased across the groups fed increasing dosages of the by determining oocysts shedding/ cycling. Oocysts per gram composition . were determined for each sample . Table 17 and 18 provide the results . As can be seen in Table 17 and 18 , the combi TABLE 15 nation of 250 ppm composition and 68 ppm Monensin resulted in a substantial reduction in the number of oocysts Feed Adj. Avg. Wt 30 detected , compared to the control and to the composition or Treatments Intake FCR Gain Monensin individually . Day 14 TABLE 17 1. O ppm Composition D 0 -42 18 . 05ab 1 . 525ab 0 . 220ab 2 . 250 ppm Composition D 0 -42 17 .60b 1 .523ab 0 .214b 35 Feed Adj. Wt. 3 . 500 ppm Composition D 0 -42 19 .01a 1 . 514ab 0 . 236a Treatment Intake FCR Gain (kg ) 4 . 750 ppm Composition D 0 -42 18 . 26ab 1 .485b 0 .230ab 5 . 1000 ppm Composition D 0 -42 18 .65ab 1 . 541a 0 . 228ab Day 14 Day 42 1 . No Additive 20 . 71a 1 .536a 0 . 258a 1. O ppm Composition D 0 -42 141. 69ab 1 . 782a 1. 745bc 40 2 . 250 ppm Composition D 0 -42 20 . 09b 1 .495ab 0 . 257a 2 . 250 Composition ppm D0 - 42 136 . 15b 1 .751 ab 1 . 705c 3 . Monensin 68 ppm D 0 -42 20 .046 1 . 473b 0 . 261a 3 . 500 Composition ppm D 0 - 42 145 .08a 1 .754ab 1 . 825a 4 . Composition + Monensin D 0 -42 19 . 87b 1 . 474b 0 . 257a 4 . 750 Composition ppm D 0 -42 140 .80ab 1 .714b 1 . 793ab Day 28 5 . 1000 Composition ppm D 0 -42 143 .14a 1 . 747ab 1 . 810ab 1 . No Additive 52. 23a 1 . 694a 0 . 652b “ D ” = days ; letters " ," " b ,” and “ c ” are used to indicate break points based on statistical 45 2 . 250 ppm Composition D 0 -42 52 .31a 1 .570b 0 .704a analysis and thereby provide an indication of statistically significant differences between 3 . Monensin 68 ppm D 0 - 42 51. 81a 1 . 562b 0 . 703a observed values . 4 . Composition + Monensin D 0 -42 53. 08a 1 .537b 0 . 729a Day 42 TABLE 16 1 . No Additive 125 .416 1 . 793a 1 . 547c 2 . 250 ppm Composition D 0 -42 127 . 33ab 1. 731b 1 .616b Treatments E .G . E .M . E . A . Total 50 3 . Monensin 68 ppm D 0 -42 124 . 77b 1 .707b 1 . 614bc Oocysts per gram fecal material Day 14 4 . Composition + Monensin D 0 -42 130 . 13a 1 .689b 1 .691a " D " = days ; letters " , " " b , " and " c " are used to indicate break points based on statistical 1 . O ppm Composition D 0 -42 172ab 819a 1010a 2001a analysis and thereby provide an indication of statistically significant differences between 2 . 250 ppm Composition D 0 -42 114ab 1086a 810a 2011a observed values . 3 . 500 ppm Composition D 0 -42 105b858a 943a 1906a 55 4 . 750 ppm Composition D 0 - 42 152ab 918a 753a 1820a 5 . 1000 ppm Composition D 0 - 42 286a 772a 734a 1791a Oocysts per gram fecal material Day 21 TABLE 18 Treatment E . gallo . E . mel. E . aden . Total 1 . O ppm Composition D 0 -42 9119a 19753a 45127a 73999a 2 . 250 ppm Composition D 0 -42 8652a 18666ab 45070a 72388a Oocysts per gram fecal material D 14 3 . 500 ppm Composition D 0 -42 12320a 15827ab 33236ab 61383ab 60 4 . 750 ppm Composition D 0 -42 8623a 17714ab 38219ab 64556ab 1 . No Additive 571a 1579a 593ab 2742a 5 . 1000 ppm Composition D 0 - 42 5269a 9481b 54498b 39248b 2 . 250 ppm Composition 363ab 1164ab 867a 2394ab Oocysts per gram fecal material Day 28 D 0 - 42 3 . Monensin 68 ppm 430ab 786b 356ab 1571bc 1 . O ppm Composition D 0 -42 505a 2020a 362a 2887a D 0 - 42 2 . 250 ppm Composition D 0 -42 429a 1953a 4862 2868a 65 4 . Composition + 237b 519b 304b 1060a 3 . 500 ppm Composition D 0 - 42 2 57a 1639a 257a 2153a Monensin D 0 - 42 US 10 ,413 ,581 B2 35 36 TABLE 18 - continued name MAGNI- PHI by Phibro Animal Health Corporation . The study comprised four treatments shown in Table 19. Treatment E . gallo . E . mel . E . aden . Total Oocysts per gram fecal material D 21 TABLE 19 1 . No Additive 674a 10405a 1364a 12443a Cages / 2 . 250 ppm Composition 889a 56626 793b7344b Coccidial Clostridium Treat D 0 - 42 Treatment Challenge perfringens ment 3 . Monensin 68 ppm 623a 2549c 237bc 3409c D 0 - 42 Ti Nonmedicated DOT 14 No 4 . Composition + 515a 1653c 1850 20530 10 T2 Nonmedicated DOT 14 DOT 19 , 20 , Monensin D 0 -42 and 21 Oocysts per gram fecal material D 28 T3 250 ppm Composition DOT 14 DOT 19 , 20 , (DO - D 28 ) and 21 1 . No Additive 259a 252a 311a 823a T4 500 ppm Composition DOTD 14 DOT 19 , 20 , 8 2 . 250 ppm Composition 200a 148ab 59b 408b ( D 0 - D 28 ) and 21 D 0 -42 15 “ D ” = day ; DOT = day of treatment 3 . Monensin 68 ppm 119a 74b 29b 252b D 0 - 42 4 . Composition + 30a 22b 15b 67b All birds were weighed on day of treatment (DOT ) O , 14 , Monensin D 0 - 42 21, and 28 . Feed was weighed in on DOT 0 and remaining " D " = days ; " E . gallo . ” = E . gallopavonis ; " E . mel. " = E . meleagrimitis; " E . aden " = E . feed was weighed on DOT 14 , 21, and 28 . 3 . Feed and water adenoeides ; letters a , " " b , " and " c " are used to indicate break points based on statistical 2020 were given ad libitum . On DOT 14 , all birds were orally analysis and thereby provide an indication of statistically significant differences between inoculated with about 5 ,000 oocysts of E . maxima . Starting observed values. on DOT 19 , all birds except Treatment 1 were given a broth culture of C . perfringens about 108 cfu /ml . The birds were Example 11 administered a fresh broth culture once daily for 3 days (on 25 DOTs 19 , 20 , and 21 ) . In this example , the effect of a composition comprising On DOT 21 , three birds from each cage were selected , Quillaja saponaria and Yucca schidigera on Necrotic sacrificed , weighed , and examined for the degree of pres Enteritis caused by Clostridium perfringens in Broiler ence of Necrotic Enteritis lesions. The scoring was based on Chickens was determined . In some embodiments , the com a 0 to 3 score , with O being normal and 3 being the most position was a commercial product sold under the trade severe . Table 20 provides the results . TABLE 20 Day 14 Feed Adj . Wt. Treatment Intake FCR Gain 1 . No Addit To CP 3 . 316a 1 . 663a 0 . 242a 2 . No Additive , CP 3 .065ab 1 . 658a 0 . 226a 3 . 250 ppm Composition , CP 2 . 885b 1 . 521b 0 .232a 4 . 500 ppm Composition , CP 3 . 213ab 1 .597ab 0 . 244a Feed Intake Feed Conversion Weight Gain (kg ) Treatment D 0 -21 D 14 -21 D 0 -21 D 14 - 21 D 0 - 21 D 14 -21 1 . No Additive , No CP 6 .211a 2 . 895a 2 .062b 1 . 964b 0 .378a 0 . 185a 2 . No Additive , CP 5 . 906ab 2 . 841a 2 . 312a 2 . 516a 0 . 332a 0 . 151b 3 . 250 ppm Composition , CP 5. 5196 2. 634a 2 .0546 2 .215ab 0. 351a 0 . 165ab 4 . 500 ppm Composition , CP 6 .137a 2. 924a 2 .094b 2. 147b 0 . 369a 0. 174ab Feed Intake Feed Conversion Weight Gain (kg ) Treatment D 0 -28 D 14 -28 D 0 - 28 D 14 -28 D 0 -28 D 14- 28 1 . No Additive , No CP 8 .372a 5 .057a 1. 9506 1 .834b 0 .652a 0 . 460a 2 . No Additive, CP 7 . 720ab 4 .655a 2 .212a 2 . 265a 0 . 530a 0 . 349b 3 . 250 ppm Composition , CP 7. 3556 4. 470a 1 .939b 1 . 945b0 .638a 0 .452ab 4 . 500 ppm Composition , CP 8 .093ab 4 . 881a 1. 934b 1 .8586 0 .627a 0 .432ab Necrotic Enteritis

Treatment Lesion % NE Mortality 1 . No Additive , No CP 0 .0b 0 .0b 2 . No Additive , CP 0 .6a 9 . 4a 3 . 250 ppm Composition , CP 0 .6a 1 .6ab 4 . 500 ppm Composition , CP 0 .5a 4 . 7ab

" D " = days: " CP ” = C . perfringens: " NE " = Necrotic Enteritis ; letters " a , " " b , " and " c " are used to indicate break points based on statistical analysis and thereby provide an indication of statistically significant differences between observed values . US 10 ,413 ,581 B2 37 38 Example 12 TABLE 22 Trophozoite Scores - age 13 days In this example , the effect of a composition comprising Wilcoxon /Kruskal -Wallis Test ( Rank Sums) P = 0 .0334 Quillaja saponaria and Yucca schidigera on Cochlosoma anatis infections in turkeys was determined . In some P - value embodiments , the composition was a commercial product Treatment Min -Max Median ( Dunn ' s ) sold under the trade name MAGNI- PHI by Phibro Animal Positive 0 - 4 250 ppm 0 - 3 0 .0868 Health Corporation . To assess the efficacy of the composi 500 ppm 0 - 3 1 . 0000 tion , birds were treated with 0 (negative and positive con - 10 750 ppm 0 - 3 0 . 16141 trols ), 250 , 500 , 750 and 1000 ppm of the composition 1000 ppm 0 - 1 0 . 0438 beginning on the day -of - hatch . The turkeys were then chal lenged with about 1x10° Cochlosoma anatis trophozoites by oral gavage at age 10 days. Twenty nine birds were left TABLE 23 untreated and unchallenged to serve as a negative control. At 15 age 13 and 16 days ( 3 and 6 days post- challenge ), birds were Trophozoite Scores - age 16 days euthanized and samples collected . Wilcoxon /Kruskal - Wallis Test ( Rank P - value Results Treatment Min -Max Median (Dunn ' s ) Mortality : 20 Positive 0 - 4 Mortality was collected pre - and post -challenge ( Table 250 ppm 0 - 4 N 21 ) . High mortality was observed in the 250 ppm ( 10 . 3 % ) 500 ppm 0 - 4 750 ppm 0 - 4 2 . 5 and 750 ppm ( 24. 1 % ) MP groups pre - challenge ; however, 1 there was no mortality for these groups post - challenge . 1000 ppm 0 - 4 Post -mortem exams indicated that the mortality was primar- 25 Fecal Scores : ily attributed to a failure to consume food ( i . e . starve -outs ) . Fecal samples were collected from five birds selected at random by placing the birds on a clean surface and waiting TABLE 21 until they defecated . Theses samples were then scored for Mortality Mortality 30 enteritits ( 0 = firm fecal sample , 1 = lose fecal sample , 2 =mod Pre - Challenge Post- Challenge erate diarrhea , 3 = severe diarrhea ). At age 10 and 13 days, Treatment (1 - 10 days ) ( 11- 16 days ) Total minimal enteritis was observed , but by age 16 days , mod Negative erate to severe enteritis had developed in some birds ( FIG . Positive 48 ) . The fecal scores were highly variable and no significant 250 ppm 35 differences were found for the treated groups when com 500 ppm pared to the positive control group ( Tables 24 and 25 ) . 750 ppm 1000 ppm TABLE 24

40 Fecal Scores - age 13 days Body Weight: Wilcoxon /Kruskal - Wallis Test ( Rank Sums) P = 0 . 1381 Body weights were collected before challenge ( age 1 and P - value 10 days ) and after challenge (age 13 and 16 days ) . A Treatment Min -Max Median ( Dunn ' s ) significant decrease in body weight was observed at age 13 Positive 0 - 0 and 16 days for the 500 ppm and 1000 ppm treated groups 250 ppm 0 - 0 500 ppm 0 - 2 | when compared to the negative control group ( FIG . 46 ). 750 ppm 0 - 1 However , no significant differences were observed for these 1000 ppm 0 - 3 ages or treatment groups when compared to the positive control group . With reference to FIG . 46 , treatments not so connected by the same letter are significantly different. TABLE 25 Trophozoite Scores : Fecal Scores - age 16 days Gastrointestinal samples were collected at meckel' s diver Wilcoxon /Kruskal - Wallis Test (Rank Sums) P = 0 .5920 ticulum and scored for the prescence of trophozoites ( 0 = 0 trophozoites , 1 = 1 - 10 trophozoites , 2 = 11 - 50 trophozoites, P - value 3 = 50 - 100 trophozoites , 4 = > 100 trophozoites ) . There Treatment Min -Max Median (Dunn 's ) appeared to be a dose dependent reduction in the trophozoite Positive 0 - 3 250 ppm 0 - 1 score for composition - treated birds at both 13 ( 3 days PI) 500 ppm 0 - 1 and 16 ( 6 days PI) days of age (FIG . 47 ) . There was a 60 750 ppm 0 - 0 significant decrease in the the number of trophozoites for the 1000 ppm 0 - 3 1000 ppm treated group when compared to the positive control at age 13 days ( Table 22 ) . There were no significant Intestinal Lesion Scores : differences at age 16 days , however, the data indicates that Sections of the small intestine were scored for necrotic the median trophozoite scores are trending lower for the 65 lesions and inflammation associated with enteritis (0 = no composition -treated birds when compared to the positive lesions , 1 = 1 - 2 focal lesions, 2 = 2 - 5 focal lesions, 3 = moder control birds ( Table 23 ) . ately coalescing lesions, 4 = severely coalescing lesions) . No US 10 , 413 , 581 B2 39 40 significant differences were observed for lesions in the TABLE 30 duodenum (FIG . 49 , Tables 26 and 27 ) or jejunum (FIG . 50 , Tables 28 and 29 ) at either age 13 or 16 days . In the ileum Ileum Scores - age 13 days there was a significant increase in the lesion score at age 16 Wilcoxon /Kruskal - Wallis Test (Rank Sums) P = 1 , 000 days for the 500 ppm group compared to the positive control 5 P - value (Dunn 's test : P = 0 .0148 ) , no other significant differences Treatment Min -Max Median ( Dunn ' s ) were detected (FIG . 51, Tables 30 and 31 ) . Positive 0 - 0 250 ppm 0 - 0 TABLE 26 500 ppm 0 - 0 10 750 ppm 0 - 0 1000 ppm 0 - 0 11111 Duodenum Scores - age 13 days Wilcoxon /Kruskal -Wallis Test (Rank Sums) P = 0 .2175 TABLE 31 15 P - value Ileum Scores - age 16 days Treatment Min -Max Median (Dunn 's ) Wilcoxon / Kruskal- Wallis Test ( Rank Sums ) P = 0 .0107 P - value Positive U Treatment Min -Max Median ( Dunn 20 250 ppm 0 - 1 Positive 0 - 1 500 ppm 0 - 2 250 ppm 0 - 1 1 .0000 500 ppm 0 . 0148 750 ppm 0 - 1 750 ppm 0 - 1 0 . 9948 1000 ppm 0 - 1 1000 ppm 0 - 1 1 .0000 25

TABLE 27 SUMMARY Duodenum Scores - age 16 days Body weights were significantly decreased for the 500 Wilcoxon /Kruskal - Wallis Test (Rank Sums) P = 0 . 0535 30 ppm and 1000 ppm composition groups at both age 13 days and 16 days when compared to the negative control; how P - value ever, a significant decrease was not observed when com Treatment Min -Max Median pared to the positive control. This data indicates that the C . (Dunn 's ) anatis challenge resulted in a reduction in body weights . Positive 0 - 2 35 Reduced body weights are observed in naturally infected 250 ppm 0 - 2 commercial turkeys and thus highlights the usefulness of 500 ppm 0 - 2 this model for assessing potential treatment strategies . At 750 ppm 0 - 1 age 13 days, trophozoite scores indicated that the positive 1000 ppm 0 - 1 control and composition treatment groups were successfully TITUT 40 infected . There was also a significant decrease in the tro phozoite score for the 1000 ppm group compared to the positive control. This data shows that composition treatment TABLE 28 can have an impact on C . anatis infections. At 16 days , there Jejunum Scores - age 13 days were no significant differences in the composition treatment Wilcoxon /Kruskal -Wallis Test ( Rank Sums) P = 0 . 3856 45 groups compared to the positive control; however , a clear trend was observed which indicated a reduction in tropho P - value zoites for composition treated birds. C . anatis infected birds Treatment Min -Max Median (Dunn 's ) developed enteritis following challenge ; however, no sig Positive 0 - 0 nificant differences were detected for fecal scores from 250 ppm 0 - 1 500 ppm 0 - 0 50 treatment groups when compared to the positive control. For 750 ppm 0 - 0 intestinal scores there were no significant differences in the 1000 ppm 0 - 0 lesions of the doudenum or jejumun of composition treated groups when compared to the positive control group . There was an increase in the lesion scores in the ileum of the 500 55 ppm treated group compared to the positive control, but TABLE 29 since no other differences were observed , the reasons for this Jejunum Scores - age 16 days increase are difficult to determine. In summary , composition Wilcoxon /Kruskal - Wallis Test (Rank Sums) P = 0 . 7610 treatment decreased trophozoites in the gastrointestinal tract of turkeys . The composition therefore could be used to P - value 60 reduce the impact of field infections and the trophozoite Treatment Min -Max Median ( Dunn ' s ) burden in commercial turkeys . Positive 0 - 3 250 ppm 0 - 2 Example 13 500 ppm 0 - 2 0 . 5 750 ppm 0 - 1 0 . 5 1000 ppm 0 - 1 65 In this example , the effect of a composition comprising Quillaja saponaria and Yucca schidigera on the microbiome of turkeys was determined . In some embodiments , the US 10 ,413 ,581 B2 42 composition was a commercial product sold under the trade And at day 84 significant decreases in E . coli and also name MAGNI- PHI by Phibro Animal Health Corporation . Enterococcus cecorum were observed (FIGS . 88 - 91 ) . And To assess the efficacy of the composition microbiome pro an increase in Lactobacillus reuteri was detected (FIGS . 92 filing was performed on whole gut samples from turkeys and 93 ) . administered the composition . In total, 121 samples were 5 Additionally, the amounts of specific bacteria were exam sequenced by amplifying the V4 region of the 16S rRNA ined across time points to validate some of the observations target from extracted DNA for each sample. This generated seen in significantly changed taxa . E . coli was decreased at 3 ,023 ,527 bp of data with the average number of sequences all time points except day 32 (FIGS . 94 - 99 , increasing in per sample at 24 , 987 ( range 13 , 201 to 38 , 247 ) . Sample were age ) . And , segmented filamentous bacteria ( Candidatus then analyzed using an open reference OTU --picking picking 10 Arthromitus) increased in treatment on day 7 , 14 , and 21 approach in QIIME followed by analyses in R statistical ( FIGS . 100 - 103 ) . package. Additionally , the bacterial community diversity of control versus treatment at each time point was examined , and is Results illustrated in FIGS. 104 - 109 . Overall , the results were non Initially , bird age was examined as a factor in bacterial 15 significant and varied between time points , suggesting there community composition . As expected , there was a clear was not a significant change in bacterial diversity between age -dependent progression of the bacterial community as control and treatment groups . illustrated in the PCoA plot in FIG . 52 . Table 32 provides twenty bacterial species identified in The same PCoA plot was then colored by treatment the samples , grouped by age and treatment. instead ofby age (FIG . 53 ). There was not a clear distinction 20 between the bacterial communities between control and TABLE 32 treatment groups, indicating that the differences needed to be examined at the individual bacterial species or group level. Stan - Composi - Stan - Composi Differences in taxa were identified between the control dard D 03 tion D 03 dard D 07 tion D 07 group and treatments groups in samples taken on days 3 , 7 , 25 Lactobacillus 0 . 6 0 . 8 567 . 8 264 aviarius 14 , 21, 32 , and 84. On day 3 , significant enrichment of Lactobacillus 13 . 1 216 . 2 1441 . 6 736 . 4 Lactobacillus reuteri and significant decrease in Clostridium reuteri species were identified (FIGS . 54 -57 ) . Romboutsia 0 . 4 0 . 3 0 . 7 0 . 7 At day 7 , there were significant decreases in cyanobac Lactobacillus 16 . 1 515 . 8 195 . 5 306 . 5 salivarius terial sequences (FIGS . 58 -59 ), Enterococcus species Lactobacillus 688 . 3 538 . 7 274 . 2 275 . 7 (FIGS . 60 and 61 ) and Streptococcus species (FIGS . 62 and johnsonii 63) . The decrease in cyanobacterial sequences were actually Lactobacillus 85 . 4 51. 5 251 . 8 107. 9 acidophilus not indicative of cyanobacteria , but rather they indicated that Lactobacillus 462. 7 367 181 .7 182 . 7 there was undigested feed containing plant materials . Thus , 28 gasseri a decrease in the cyanobacterial sequences suggested that Ruminococcus 439 . 2 726 . 2 287 . 1 659 . 3 Ruminococcus2 433 . 8 404 . 9 163. 2 165 there was less undigested feed in the gut at time of sampling Oscillospira 261. 6 403 . 1 127 . 8 238 . 5 in the treatment groups. bacterium 0 .01 0 .01 2 . 1 0 . 01 At day 14 , a significant increase in Lactobacillus reuteri Faecalibacterium 278 . 1 202 58 . 5 113 . 6 was again observed in the treatment group (FIGS . 64 and 40 prausnitzii Ruminococcus 3 439 22. 5 131. 4 137 . 4 65 ) . Additionally , there was a significant enrichment in Escherichia coli 614 .5 370 . 4 121. 4 99 .7 Peptostreptococcaceae , which includes butyrate producing Rikenellaceae 1 . 2 0 . 4 759 4 . 5 Faecalibacterium 10 . 8 1 . 3 554 0 . 4 bacteria that have been shown to be positively correlated prausnitzii2 with improved gut health (FIGS . 66 and 67 ) . Ruminococcus4 394 . 4 392. 3 66 . 8 222 .7 At day 21, significant decreases in Clostridiaceae , 45 StreptococcusStrept 139 . 3 86 . 7 168 . 2 698 . 8 Corynebacterium species , Staphylococcus species, and Faecalibacterium 184 . 3 58. 2 81 .7 129. 8 Streptococcus species (FIGS . 68 -75 ) were observed , all of prausnitzii3 which contain pathogenic species of bacteria . In contrast , a Clostridiales 370 . 7 238 111 . 1 147. 8 significant increase in segmented filamentous bacteria (Can Stan - Composi Stan - Composi didatus Arthromitus ) was detected ( FIGS . 76 and 77 ) . The 50 dard D 14 tion D 14 dard D 21 tion D 21 earlier appearance of Candidatus Arthromitus in turkey Lactobacillus 1963. 9 1612 . 8 1354 889 . 8 flocks has been a strong biomarker of enhanced perfor aviarius mance , so the earlier appearance and higher abundance of Lactobacillus 573. 7 11521152 569. 1 547 . 8 this bacteria in the treatment groups suggested enhance reuteri performance and accelerate maturation of the microbiota in 55 Romboutsia 0 . 5 0 . 3 1 . 8 1 . 3 Lactobacillus 628 . 8 312 . 8 237 539 . 9 the treatment birds. salivarius By day 32, segmented filamentous bacteria (Candidatus Lactobacillus 755 . 4 525 . 4 519 341 . 6 Arthromitus ) had appeared in the control group (FIGS . 78 johnsonii Lactobacillus 958 . 2 1241. 6 97 .4 419 . 6 and 79 ) . However, the abundance was lower than was acidophilus observed in the treatment group 11 days earlier. This again 60 Lactobacillus 503. 8 345 . 8 297 192 suggested an earlier appearance and increased abundance of gasseri these bacteria in the treatment group . Also , a significant Ruminococcus 69 . 7 73 . 7 61. 3 133 Ruminococcus2 109 . 8 188 . 8 214 349 . 4 decrease in Corynebacterium species, E . coli, and Staphy Oscillospira 125 . 8 223 . 4 310 . 1 379 . 4 lococcus species ( FIGS . 80 -- 85 ) was observed . And anan Bifidobacterium 139 . 1 170 .7 212 . 3 147. 8 increase in Peptostreptococcaceae was detected (FIGS . 86 65 Faecalibacterium 140 . 7 68 . 6 369 . 5 446 . 2 and 87 ) , including butyrate producing bacteria that are prausnitzii shown to be positively correlated with improved gut health . US 10 , 413 ,581 B2 43 44 TABLE 32 - continued than 0 ppm to 5 , 000 ppm of the first composition comprising Quillaja saponaria , Yucca schidigera , or a combination Ruminococcus3 132 . 3 223 . 7 121 . 4 223 . 2 thereof ; and the second composition ; wherein the combina Escherichia coli 166 122 . 7 109 . 1 66 Rikenellaceae 54 69 . 3 415 211 . 9 tion is formulated for administration to an animal other than Faecalibacterium 318. 6 256 . 4 148 . 2 65 . 6 5 a chicken or turkey . prausnitzii2 In some embodiments , the combination is formulated for Ruminococcus4 53 . 2 29 . 2 107 . 6 93 . 3 Streptococcus 3 . 3 3 . 6 12 . 4 2 . 3 avian other than chicken or turkey , livestock , aquaculture Faecalibacterium 85 . 7 20 282 . 4 229 . 4 species , domesticated animals , ruminants , or ungulates . In prausnitzii3 some embodiments the chicken is a broiler chicken . Clostridiales 25. 8 152 . 8 78 . 3 259 . 5 10 In some embodiments , the first composition is formulated Stan Composi Stan for administration to an animal other than a chicken or dard D 32 tion D 32 dard D 84 turkey and the amount of the first composition ranges from 50 ppm to 5 ,000 ppm . In some embodiments , the first Lactobacillus 2123 . 2 1173 . 7 1494 . 4 composition is formulated for administration to an animal aviarius Lactobacillus 263 44 . 3 205 . 8 other than a chicken or turkey and the amount of the first reuteri composition ranges from 50 ppm to 2 ,500 ppm . Romboutsia 12 63 . 4 2581 . 8 In any or all of the above embodiments , the first compo Lactobacillus 744 . 3 997 . 3 110 . 3 sition comprises a mixture of Quillaja saponaria and Yucca salivarius schidigera in a ratio ranging from 70 : 30 Quillaja saponaria : Lactobacillus 54 . 6 11 . 2 263. 5 johnsonii 20 Yucca schidigera to 90 : 10 Quillaja saponaria : Yucca schi Lactobacillus 112 . 4 685 . 1 118 . 2 digera . acidophilus In any or all of the above embodiments , the second Lactobacillus 40 . 1 5 . 5 148 . 6 gasseri composition comprises 10 ppm to 30 ppm Virginiamycin . Ruminococcus 36 . 6 75 . 8 31. 5 In any or all of the above embodiments , the second Ruminococcus2 377 . 6 151. 7 13 . 1 25 composition comprises 25 ppm to 90 ppm Salinomycin . Oscillospira 173 . 2 117 . 9 56 . 1 In any or all of the above embodiments , the combination Bifidobacterium 875 .7 557 . 6 133. 7 Faecalibacterium 137 194 . 6 101. 3 can comprise a third composition comprising a vaccine . In prausnitzii some embodiments , the vaccine is a coccidiosis vaccine Ruminococcus3 270 92 . 4 146 comprising oocysts derived from Eimeria acervulina , Eime Escherichia coli 180 . 3 78 . 7 55 . 4 30 ria mivati, Eimeria maxima, Eimeria tenella , Eimeria neca Rikenellaceae 110 . 9 329 . 4 19 . 3 trix , Eimeria mitis, Eimeria praecox , Eimeria brunetti, Faecalibacterium 249 . 2 220 . 7 9 . 4 prausnitzii2 Eimeria hagani, or combinations thereof . Ruminococcus4 34 . 1 92 . 2 82 . 6 In any or all of the above embodiments , the Quillaja Streptococcus - 6 . 4 2 . 7 363. 9 saponaria is a Quillaja saponaria plant extract, the Yucca Faecalibacterium 226 . 6 192 . 9 28 . 9 prausnitzii3 35 schidigera is a Yucca schidigera plant extract, or both . In Clostridiales 59 .5 some embodiments , the Quillaja saponaria plant extract 25 comprises at least one saponin , polyphenol, antioxidant, resveratrol or any combination thereof. In some embodi ments, the Yucca schidigera plant extract comprises at least Conclusion 40 one saponin , polyphenol, antioxidant , resveratrol or any combination thereof. The relative abundance of several bacterial taxa were In any or all of the above embodiments , the first and changed in birds that were fed a composition comprising second compositions are admixed to form an admixed Yucca schidigera and Quillaja saponaria , compared to birds composition . that were not fed the composition . Some changes occurred 45 In any or all of the above embodiments , the first compo at specific times , and other changes occurred across several sition , the second composition , and third composition are time points . This suggests that biologically meaningful admixed to form an admixed composition . In some embodi changes to the microbiome occurred as a result of admin - ments , the admixed composition is further admixed with a istration of the composition . Specifically, changes included feedstuff to form a feedstuff admixture . In some embodi reductions in common pathogens such as E . coli , 50 ments , the components of the admixed composition , the Clostridium spp . , Enterococcus spp . , Staphylococcus spp ., feedstuff admixture , or both , are sized , concentrated , or and Streptococcus spp ., and enrichment of Lactobacillus diluted to facilitate admixing , facilitate administration to an reuteri and in the abundance of segmented filamentous animal, or combinations thereof. bacteria . Overall, these specific modifications to the gut In any or all of the above embodiments, the combination microbiome indicate that administration of the composition 55 can further comprise a vitamin , a trace mineral, a bulking may reduce pathogen load in the gut and enrich beneficial agent, a carrier, a colorant , a taste enhancer, or any combi bacteria that accelerate gut microbiome maturation . nation thereof. In any or all of the above embodiments , the combination Overview of Several Embodiments can further comprise corn , soybean meal, wheat, barley, rye , 60 canola , corn oil, limestone, salt , distillers dried grains with In some embodiments disclosed herein , the combination solubles (DDGS ), dicalcium phosphate , sodium sesquicar can comprise 200 ppm to 5 , 000 ppm of a first composition bonate , methionine source , lysine source , L - threonine , cho comprising Quillaja saponaria , Yucca schidigera , or a com - line , or any combination thereof. bination thereof; and a second composition comprising an In any or all of the above embodiments , the combination antimicrobial agent, an antibiotic , an anticoccidial agent, or 65 is administered to an animal that has been or is at risk of combinations thereof; wherein the combination is formu - being exposed to coccidia . In some embodiments , the coc lated for administration to a chicken or turkey ; or greater cidia are ionophore - resistant coccidia . US 10 ,413 , 581 B2 45 46 In some embodiments , the combination comprises 200 In any or all of the above embodiments , the administration ppm to 300 ppm of a first composition comprising Quillaja of the combination to the animal has a beneficial effect on saponaria , Yucca schidigera , or a combination thereof; and the health of the animal relative to an animal not adminis 10 ppm to 70 ppm of an antibiotic , antimicrobial, anticoc tered the combination . In some embodiments , the beneficial cidial, or combination thereof; and wherein the combination 5 effect on the health of the animal is a beneficial effect on the is formulated for administration to a domestic fowl. digestive system of the animal. In some embodiments , the method comprises improving feed conversion rate in animal Also disclosed herein are embodiments of methods com in a commercial feed operation by administering at least prising administering a combination as disclosed herein to once daily a mixture comprising a feedstuff , an antimicro an animal at least once daily from day of age and for a timeIn 10 bial , an antibiotic , an anticoccidial agent , or a combination period sufficient to promote a beneficial health effect. In thereof, and 200 ppm to 5 , 000 ppm Quillaja saponaria , some embodiments , the combination comprises 200 ppm to Yucca schidigera , or both , wherein the mixture improves the 5 ,000 ppm of a first composition comprising Quillaja animal' s feed conversion rate by greater than 0 . 5 % up to at saponaria , Yucca schidigera , or a combination thereof ; and least 5 % relative to an animal that is not administered the a second composition comprising an antimicrobial agent, an 15 mixture . In some embodiments , the first composition com antibiotic , an anticoccidial agent, or a combination thereof, prises a mixture of Quillaja saponaria and Yucca schidigera and wherein the combination is administered to a chicken or in a ratio ranging from 70 : 30 Quillaja saponaria : Yucca turkey . In some embodiments , the combination comprises schidigera to 90 : 10 Quillaja saponaria : Yucca schidigera . greater than 0 ppm to 5 , 000 ppm of a first composition Also disclosed herein are embodiments of a method for comprising Quillaja saponaria , Yucca schidigera , or a com - 20 making a combination , comprising providing a first compo bination thereof ; and a second composition comprising an s ition comprising Quillaja saponaria , Yucca schidigera, or antimicrobial agent , an antibiotic , an anticoccidial agent, or both ; providing a second composition comprising an anti combinations thereof , and wherein the combination is microbial agent , an antibiotic , an anticoccidial agent, or a administered to an animal other than a chicken or turkey . combination thereof; and combining the first and second In any or all of the above embodiments , the first compo - 25 compositions . In some embodiments , the amount of the first sition comprises a mixture of Quillaja saponaria and Yucca composition ranges from greater than 0 ppm to 5 , 000 ppm . schidigera in a ratio ranging from 70 : 30 Quillaja saponaria : In some embodiments , the amount of the first composition Yucca schidigera to 90 : 10 Quillaja saponaria : Yucca schi ranges from 50 ppm to 5 , 000 ppm . digera . In any or all of the above embodiments , the Quillaja In any or all of the above embodiments, the first and 30 saponaria is a Quillaja saponaria plant extract, the Yucca second compositions are administered substantially simul- schidigera is a Yucca schidigera plant extract, or both . In taneously . some embodiments , the Quillaja saponaria plant extract In any or all of the above embodiments, the first and comprises at least one saponin , the Yucca schidigera plant second compositions are administered sequentially , in any extract comprises at least one saponin , or both . order. 35 In any or all of the above embodiments , the first compo In any or all of the above embodiments , the method can sition comprises a mixture of Quillaja saponaria and Yucca further comprise administering the first composition and the schidigera in a ratio ranging from 70 : 30 Quillaja saponaria : second composition in combination with a feedstuff . Yucca schidigera to 90 : 10 Quillaja saponaria : Yucca schi In some embodiments, the combination is administered to digera . a chicken or turkey and the feedstuff is provided in an 40 In any or all of the above embodiments , the method amount ranging from at least 7 lbs to 10 lbs of a feedstuff per further comprises admixing the combination with a feedstuff chicken or turkey . In some embodiments , the first compo - to form an admixed feedstuff. In some embodiments , the sition , the second composition , and the feedstuff are admin - method further comprises formulating the first and / or second istered substantially simultaneously. In some embodiment, compositions for mixture with the feedstuff to provide a the first composition , the second composition , and the 45 substantially homogeneous admixed feedstuff . feedstuff are administered sequentially , in any order. In any or all of the above embodiments , the method In any or all of the above embodiments , the method further comprises combining the first composition , the sec comprises administering a third composition comprising a ond composition , or both with a third composition compris coccidiosis vaccine comprising oocysts derived from Eime- ing a vaccine . In some embodiments , the first composition , ria acervulina , Eimeria mivati , Eimeria maxima , Eimeria 50 second composition , and third composition are admixed tenella , Eimeria necatrix , Eimeria mitis , Eimeria praecox , simultaneously or sequentially . Eimeria brunetti, Eimeria hagani, or combinations thereof. In view of the many possible embodiments to which the In some embodiments , the first composition , second com - principles of the present disclosure may be applied , it should position , third composition , and the feedstuff are adminis - be recognized that the illustrated embodiments are only tered substantially simultaneously . In some embodiments , 55 preferred examples of the disclosure and should not be taken the first composition , second composition , third composi - as limiting the scope of the claimed invention . We claim as tion , and the feedstuff are administered sequentially , in any our invention all that comes within the scope and spirit of the order. following claims. In any or all of the above embodiments , the animal other than a chicken or turkey is an avian other than a chicken or 60 We claim : turkey , a mammal, a ruminant, an ungulate , or an aquacul 1 . A combination of compositions, comprising a first ture species . In some embodiments , the chicken is a broiler composition comprising Quillaja saponaria processed plant meat- type chicken . material and / or an extract thereof and Yucca schidigera In any or all of the above embodiments , the animal has a processed plant material and / or an extract thereof in a ratio lower feed conversion rate relative to an animal not admin - 65 ranging from 70 - 90 : 10 - 30 of Quillaja saponaria : Yucca schi istered the combination . In some embodiments , the feed digera , respectively , and a second composition comprising conversion rate is improved by at least 0 . 5 % to at least 5 % . 10 ppm to 30 ppm Virginiamycin , 25 ppm to 90 ppm US 10 , 413 , 581 B2 48 Salinomycin , or combinations thereof, wherein the combi 15 . The method of claim 7 , wherein the first and second nation is formulated for administration to a chicken or compositions are administered substantially simultaneously . turkey. 16 . The method of claim 7 , wherein the first and second 2 . The combination of claim 1 , further comprising a third compositions are administered sequentially , in any order. composition comprising a vaccine . 17 . The method of claim 7 further comprising combining 3 . The combination of claim 2 , wherein the vaccine is a the first and second compositions with a feedstuff to form a coccidiosis vaccine comprising oocysts obtained from Eime mixture and administering the mixture to the chicken or the ria acervulina , Eimeria mivati , Eimeria maxima, Eimeria turkey . tenella , Eimeria necatrix , Eimeria mitis , Eimeria praecox , Eimeria brunetti, Eimeria hagani, or combinations thereof. 10 18 . The method of claim 15 , further comprising admin 4 . A combination , comprising 10 ppm to 5 ,000 ppm of a istering a third composition comprising a coccidiosis vac first composition comprising Quillaja saponaria processed cine comprising oocysts obtained from Eimeria acervulina , plantmaterial and / or an extract thereof and Yucca schidigera Eimeria mivati, Eimeria maxima, Eimeria tenella , Eimeria processed plant material and / or an extract thereof, and a necatrix , Eimeria mitis , Eimeria praecox, Eimeria brunetti , second composition comprising an antimicrobial agent , an 15 Eimeria hagani, or combinations thereof. antibiotic , an anticoccidial agent, 10 ppm to 30 ppm Vir 19 . The method of claim 18 , wherein the first composi giniamycin , 25 ppm to 90 ppm Salinomycin , or a combina tion , the second composition and the third composition are tion thereof, wherein the combination is formulated for administered substantially simultaneously, or sequentially in administration to an animal other than a chicken or turkey. any order. 5 . The combination of claim 4 , wherein the combination 20 20 . A method , comprising administering the combination comprises from 50 ppm to 2 ,500 ppm of the first composi of claim 4 to an animal other than a chicken or a turkey at tion . least once daily for a time period sufficient to promote a 6 . The combination of claim 4 , further comprising a third beneficial! health effect. composition comprising a vaccine . 21 . The method of claim 20 , wherein the animal is a 7 . A method , comprising administering the composition 25 mammal, an aquaculture species , or an avian other than a combination of claim 1 to a chicken or turkey . chicken or turkey . 8 . The method of claim 7, wherein the combination is 22 . The combination of claim 1 , wherein the Quillaja administered to the chicken or the turkey from day of age . saponaria is processed Quillaja plantmaterial and the Yucca 9 . The method of claim 7, wherein the chicken is a broiler schidigera is processed Yucca plant material. meat -type chicken . 30 23 . The combination of claim 1 , further comprising a 10 . The method of claim 7 , wherein the chicken or turkey feedstuff , Bacitracin MD , Zinc Bacitracin , Tylosin , Linco has a lower feed conversion rate . mycin , Flavomycin , Terramycin , Neo - Terramycin , penicil 11 . The method of claim 10 , wherein the feed conversion lin , tetracycline, ceftiofur , florfenicol , tilmicosin , enrofloxa rate is improved by at least 0 . 5 % to at least 5 % . cin , tulathromycin , procaine penicillin , benzathine 12 . The method of claim 7 , wherein the combinationon is 3536 penicillinpen , ampicillin , amoxicillin , spectinomycin , dihy administered at least once daily for a time period sufficient drostreptomycin , chlortetracycline , gentamicin , sulphadimi to promote a beneficial health effect . dine, trimethoprim , oxytetracycline , erythromycin , or nor 13 . The method of claim 12 , wherein the beneficial health floxacin , Monensin , Lasalocid , Narasin , Maduramicin , effect on the chicken or turkey is a beneficial effect on the Semduramicin , Laidlomycin , Nicarbazin , Maxiban , Dicla digestive system of the chicken or turkey . 40 zuril , Toltrazuril, Robenidine, Stenorol, Clopidol, Decoqui 14 . Themethod of claim 12 , wherein the beneficial health nate, DOT ( zoalene ), Amprolium , or a combination thereof . effect on the chicken or turkey comprises an earlier appear 24 . The combination of claim 1 , wherein the Quillaja ance of segmented filamentous bacteria , an increase in the saponaria is an extract and the Yucca schidigera is an abundance of segmented filamentous bacteria , an increase in extract. the abundance of Lactobacillus , or a combination thereof .