Here is a sneak preview of the forthcoming book Current Therapy in Equine Medicine, 5th edition. This chapter onprobiotics, prebiotics, and synbiotics is by J. Scott Weese.

PROBIOTICS, PREBIOTICS, AND SYNBIOTICS

J. Scott WeeseGuelph, Ontario

The equine gastrointestinal tract, particularly the largecolon and cecum, contains a complex and diverse bacterialpopulation that plays a critical role in maintenance of health.This microflora is essential for growth and survival of theanimal and is critically important for the prevention of coloni-zation or overgrowth of intestinal pathogens. The intestinalmicroflora can be protective via a number of mechanismsincluding competitive inhibition (occupation of specific envi-ronmental niches), production of inhibitory factors, modifica-tion of the local environment (production of organic acids,volatile fatty acids, hydrogen peroxide and other compounds),or effects on local inflammatory and immune responses. Dis-ruption of this microflora can result in the development ofdisease, which manifests most commonly as diarrhea. Antimi-crobial therapy commonly is implicated; however, other factorssuch as stress, diet changes, transport, or concurrent diseasemay be involved.

Because of the critical nature of this microflora and thepotentially disastrous results that can occur when it is dis-rupted, beneficially changing the microflora or preventing ad-verse changes is desirable. Modification of the intestinal mi-croflora through the administration of prebiotics, probiotics, orsynbiotics is becoming increasingly popular in human andveterinary medicine as a means to prevent or treat disease. Oneof the main factors limiting the use of probiotics in equinemedicine is the paucity of objective research. Prebiotic therapyhas received even less attention. A review of the currentliterature provides little to no guidance on how to incorporatesuccessfully these treatment options into a therapeutic plan.Studies involving other mammalian species can informative;however, interspecies variation limits direct cross-applicationof results.

PROBIOTICS

Probiotics are living microorganisms that when ingested incertain numbers exert a beneficial effect beyond that of theirnutritional value. Probiotic therapy is not a new concept.Rather it dates back to at least 1905; however, interest inprobiotic therapy has increased dramatically over the past 10 to20 years. Probiotics are an attractive, nonantibiotic, safe, andpotential efficacious treatment option in horses and other spe-cies.

The exact mechanism of action of probiotics is still un-clear. Initial theories revolved around “competitive exclusion,”in which “good” bacteria eliminated or suppressed “bad” bac-teria. Although competitive exclusion may play a role in pro-biotic therapy, it is unlikely to account for the wide array ofbeneficial effects that have been reported in other species.Alternative proposed mechanisms include antimicrobial factorproduction, immunoregulatory effects, antiinflammatory ef-fects, anticarcinogenic effects, and direct effects on the intes-tinal mucosa.

Most commercially available probiotics are non–spore-forming lactic acid bacteria, namely lactobacilli, bifidobacteria,and enterococci. A variety of strains have been demonstrated topossess beneficial (probiotic) properties. Bacilli, including Ba-cillus licheniformis, Bacillus subtilis, and Bacillus toyoi, havebeen evaluated to a more limited extent, and are less widelyavailable. One of the most attractive properties of bacilli istheir ability to form resistant spores that should be better ableto withstand the rigors of processing and storage. Nonpatho-genic strains of E. coli have been evaluated in some species asa means of competitively excluding pathogenic strains of E.coli. Probiotics containing E. coli are not available for horsesand may not be useful as the relevance of E. coli in equinegastrointestinal disease is unclear.

Yeasts also have been evaluated for probiotic properties;however, most yeast supplements act as nutritional supple-

Reprinted with permission from Elsevier Science.Copyright 2002, Elsevier Science (USA). All rights reserved.0737-0806/02/2208-0007$35.00/0doi:10.1053/jevs.2002.37109

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ments, not probiotics. Saccharomyces boulardi is a nonpatho-genic yeast shown effective for the prevention of antibiotic-associated diarrhea and treatment of recurrent Clostridiumdifficile diarrhea in people. This effect is thought to be due todirect effects on C. difficile, in addition to secretion of aprotease that affects toxins. Whether these same effects occurin horses and the dose required have not yet been reported. Inpeople, a dose of 3 � 1010 CFU/d (30 billion viable organismsper day) has been used. Presumably, a higher dose would berequired in adult horses. Kluyveromyces fragilis (marxianus)B0399 is a strain of yeast marketed for use in horses. It isclaimed that this yeast can survive passage through the stomachand have various effects in the intestinal tract of the horse. Thisspecies of yeast may have increased heat stability and survivalduring processing and storage, which would be beneficial;however, in vivo studies are lacking.

Yogurt is used commonly in humans and animals for thetreatment of enteric disease. Despite anecdotal reports of suc-cess, doubts have been raised about the efficacy of yogurt inpeople because of a number of reasons. Most yogurts containStreptococcus thermophilus and Lactobacillus bulgaricus,which are not typically considered to be probiotics because ofdestruction during passage through the intestinal tract. Somecommercial yogurt products contain specific probiotic strainsand therefore may be useful, but the low bacterial numberspresent in yogurt may limit their effectiveness. Commercialprobiotic yogurts must contain 1 � 107 CFU/mL, but this levelof growth is not present in all products. Without specific dosedetermination studies, predicting the volume of yogurt requiredfor a probiotic effect in horses is difficult. However, with ayogurt product containing 1 � 107 CFU/mL, 30 liters per daywould be required to deliver a dose of 3 � 1011 CFU/d.Although lower volumes of yogurt may be effective in somecases, using concentrated probiotic preparations containinghigher levels of bacterial growth is preferable.

Although a number of organisms have been demonstratedto possess beneficial probiotic properties, great variation existswithin species of microorganisms. Beneficial effects cannot beextrapolated between members of the same species, let alonethe same genus. Individual bacterial or yeast strains must betested to determine whether they possess beneficial properties.These include surviving passage through the stomach and smallintestine, remaining viable during processing and storage, be-ing nonpathogenic, and exerting one or more beneficial effectssuch as antimicrobial factor production, immune regulation, ordecreasing inflammation. In the absence of strain-specific invitro and in vivo testing, determination of whether a certainstrain could be beneficial is impossible. Further, some believethat probiotic organisms should originate from the intestinaltract of their target species. Although this has not been evalu-ated in horses, it seems logical that microorganisms found inhorses would likely be better adapted to survive in the intestinaltract of a horse compared with bacteria originating in otherspecies.

Lactobacillus rhamnosus strain GG (LGG) is perhaps the

best-tested human probiotic and has been demonstrated to beeffective for the prevention or treatment of a number of con-ditions. However, high doses of this organism are required toachieve intestinal colonization in adult horses. Lower doses areable to colonize the intestinal tract of foals, however, so LGGmay have potential for the prevention or treatment of diarrheicdisease in foals.

In humans, certain probiotics have been demonstrated tobe effective in a wide variety of conditions, including acuteviral and nonviral diarrhea in children, inflammatory boweldisease, “traveler’s diarrhea,” and lactose intolerance. Mixedresults have been obtained for the prevention of antibiotic-associated diarrhea and reduction of serum cholesterol levels.Preliminary research suggests that probiotics may be useful inthe treatment of atopic dermatitis, food allergy, Crohn’s dis-ease, prevention of dental caries, and stimulation of the im-mune system. Probiotics also have been shown to reduce thelevels of various fecal enzymes associated with metabolicactivation of carcinogens and mutagens.

Commercial Probiotics and Feeds ContainingProbiotics

A number of probiotic supplements are commerciallyavailable for use in horses, in the form of powders, pills,capsules, or pastes and generally include one or more speciesof Lactobacillus or Enterococcus. The numbers of viable or-ganisms that products claim to contain varies greatly, withsome containing very low and almost certainly subtherapeuticlevels. Despite the widespread availability of commercial pro-biotics in horses, little objective research supports their use. Inone study, the administration of a probiotics did not affect theshedding of salmonellae in horses’ hospitalization for colic orcolic surgery. This does not discount the potential for probiotictherapy in horses, because no indication existed that the organ-isms used in this study possessed any in vitro or in vivo effectsthat could be useful.

One of the major problems in evaluating response toprobiotics is the apparent deficiency in quality control amongmany commercial probiotics. A recent study of eight veterinaryprobiotics reported that the best product contained less than 2%of its label claim of viable numbers. Most products did notcontain one or more of the listed contents and many containedorganisms not listed on the label. The results of this study weresimilar to studies evaluating probiotics intended for human use.This makes selection of commercial probiotics difficult. Someequine products claim to be probiotics but contain only “fer-mentation products.” Fermentation products are by-products ofbacterial growth and may contain enzymes synthesized bybacteria but not necessarily live organisms. These productsclaim that enzymes produced by the lactobacilli are beneficial;however, no evidence supports these claims. Regardless, theseproducts cannot be considered probiotics if no viable organ-isms are present.

An increasing number of commercial horse feeds claim tocontain probiotic organisms. Probiotic-containing feeds repre-

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sent an easy way to administer probiotics for a prolongedperiod of time. However, whether the addition of probiotics toa feed is a realistic option is uncertain. The potential for loss ofviability exists during processing, especially when heat ormoisture are involved. Shelf-life also would be a concern withrespect to maintaining viability. A study of dog and cat foodsthat claimed to contain probiotics reported that the number ofviable organisms tended to be low and often a disparity existedbetween label claims and actual contents. Whether this was dueto improper addition of the probiotic organisms or loss ofviability during processing and storage is unclear. The appar-ently high level of supplementation that is required for anorganism to colonize the intestinal tract of an adult horse maypreclude the manufacture of probiotic-containing feeds. Probi-otic-containing creep feeds or foal supplements may be a morereasonable option because a much lower number of organismsare needed for colonization of a foal’s intestinal tract.

SafetyProbiotics are classified as “generally regarded as safe”

(GRAS) and adverse effects are reported rarely. Concerns existregarding the use of probiotics containing enterococci becausethese organisms are recognized opportunistic pathogens. Cer-tain probiotic enterococci have been proved able to transfer thegene responsible for vancomycin resistance. For this reason, amovement is growing, particularly in Europe, to stop the use ofenterococci as probiotics. The incidence of adverse effectsfrom the use of enterococci in equine probiotics is presumablyextremely low. However, because few concerns exist regardingthe use of probiotic products containing lactobacilli and bi-fidobacteria, avoiding the use of enterococci as probiotics inhorses may be reasonable. Lactobacillus rhamnosus strain GG,a human-origin probiotic, has been shown to affect intestinalantigen transport, perhaps through decreased uptake by largemolecule transport pores. If this effect occurs in foals, thetheoretical possibility exists that passive transfer of maternalantibodies could be affected. Until proven otherwise, avoidingthe use of probiotics in foals less than 24 hours of age is wise.

Clinical ApplicationA number of possible indications exist for the use of

probiotics in horses, which involve primarily gastrointestinaldisease. Probiotics should be considered for the treatment ofacute and chronic diarrhea in adult horses and foals. Whenprobiotics are coadministered with antibiotics (oral or paren-teral), the probiotic organisms may be killed. Therefore know-ing the antimicrobial resistance spectrum of probiotic organ-isms is important to determine whether coadministration withcertain drugs is feasible. This is important especially withdrugs such as metronidazole that are used commonly in thetreatment of diarrhea.

Probiotics are an attractive option for the prevention ofdisease particularly during high-risk periods (ie, antibiotic ad-ministration, concurrent disease, shipping) or during outbreaksof foal diarrhea. The role of the intestinal microflora in cases of

colic is unclear; however, some cases of colic may occur as aresult of changes in the intestinal microflora. However, theutility of probiotics for prevention of colic is questionablegiven the high dose of organism seemingly necessary forcolonization of the intestinal tract of adult horses. Probiotictherapy may be best used prophylactically during times of highrisk for the development of diarrheic disease. If probiotics areto be used for the prevention of disease during specific circum-stances, therapy should begin approximately 3 days before thehigh-risk period. Long-term prophylactic therapy may be morereasonable in foals because of the lower levels of organismrequired for colonization.

Ideally, probiotic organisms with demonstrated ability tocolonize the intestinal tract of horses and proven efficacywould be used. Until proven products become available, pro-biotic strains demonstrated to be effective in other species maybe useful; however, differences apparently exist between spe-cies in the ability of certain probiotic strains to colonize andexert effects. Appropriate dosing is important and must besupported by in vivo testing in horses. In the absence of equinestudies, very high levels of viable organisms presumably wouldbe required to colonize the intestinal tract of the adult, whereaslower levels should adequately colonize foals. Avoidance ofproducts containing enterococci may be wise because they canbe opportunistic pathogens. In addition, probiotic strains ofenterococci have been shown able to transfer antibiotic resis-tance (including vancomycin resistance) to pathogenic entero-cocci. At this point, administration of doses of 1 � 1010 CFU/d(10 billion viable organisms per day) in foals and at least 3 �1011 CFU/d (300 billion viable organisms per day) in adulthorses is recommended.

Although the quality control of many commercial productsis doubtful, only products identifying their contents to thespecies level and stating a guaranteed level of live growthshould be used. Product labels should be scrutinized carefully.If a product states only the level of growth present at manu-facturing, not by the expiration date, then it should be avoided.Storage of commercial products can affect greatly productviability. Probiotics should not be exposed to fluctuations intemperature and should be kept cool.

PREBIOTICS

A prebiotic is a nondigestible food ingredient that benefi-cially affects the host by stimulating growth and/or activity ofcertain bacterial components of the intestinal microflora. Pre-biotics are neither hydrolyzed nor absorbed in the small intes-tine, are a selective substrate for potentially beneficial organ-isms in the colon, and alter the colonic microflora in a mannerthat produces beneficial effects. A number of food ingredientscould act as prebiotics; however, the most commonly evaluatedprebiotics are those that stimulate the lactic acid bacteria (lac-tobacilli, bifidobacteria, and enterococci) component of themicroflora. These consist mainly of nondigestible frucotooli-

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gosaccharides and soybean oligosaccharides. After passingthrough the small intestine essentially unchanged, they are anutritional substrate for certain types of colonic and cecalbacteria. Fructooligosaccharides (FOS) have been evaluated inother species and, in general, increase the concentration ofcolonic bifidobacteria. The ability of lactobacilli isolates toutilize FOS is variable. At this point, little is known about therole of bifidobacteria in horses, whereas it is known horseshave a significant lactobacilli population.

Lactitol can stimulate the growth of certain lactobacilli;however, its effect in horses in unproven. Arabinogalactansupplementation was reported recently to decrease the inci-dence of diarrhea in foals in a preliminary study; however, theexact mechanism by which this was achieved is unclear andfurther research is required. Mannan-oligosaccharides are de-rived from the cell wall of the yeast Saccharomyces cerevisiaeand have been used as a poultry-feed supplement to improveproduction parameters. The mechanism of action is purportedto be adhesion and inhibition of pathogenic bacteria and im-provement of immune function rather than direct effects onintestinal microbial population. Therefore they are not prebi-otics. Mannan-oligosaccharides have been administered tohorses; however, no efficacy studies have been performed.

Prebiotics may be administered as daily or intermittentsupplements or incorporated into commercial diets. An advan-tage of prebiotic therapy over probiotic therapy is that viablemicroorganisms are not required. Viability of prebiotics shouldnot be lost during standard processing and storage, as opposedto the situation with probiotics. The safety of prebiotics has notbeen evaluated in horses. Generally, prebiotics are assumedsafe. However, alterations in the intestinal microflora couldresult in adverse effects, depending on what bacterial popula-tions are stimulated. Colic and laminitis associated with lush,spring grass may be caused by ingestion of high levels offructooligosaccharides (fructans) and subsequent effects on theintestinal microflora. The possible risks of prebiotic adminis-tration, particularly in high doses, warrant further evaluation.

SYNBIOTICS

Synbiotic describes a combination of a prebiotic and aprobiotic. The addition of an appropriate prebiotic may im-prove survival and establishment of a probiotic organism byproviding a readily available nutritional source that might notbe used by competing organisms. However, this approachcannot yet be recommended in horses pending the identifica-tion of prebiotics and probiotics with demonstrable efficacy inthe horse and compatible prebiotic/probiotic combinations.

CONCLUSION

The therapeutic use of prebiotics, probiotics, and synbiot-ics in veterinary medicine is in its infancy. Despite the wide-spread availability of these products little equine-specific re-search is underway. As a result, making educated decisionsregarding the incorporation of these products into a treatmentregimen is difficult. Given proper research, probiotics likelywill become a useful and practical therapeutic option for theequine veterinarian. Prebiotics and synbiotics may be similarlyuseful; however, their potential is less clear. Given the apparenthigh index of safety of most commercially available probiotics,they may be used as an adjunctive treatment of gastrointestinaldisease.

SUPPLEMENTAL READINGS

Collins MD, Gibson GR: Probiotics, prebiotics, and synbiotics:approaches for modulating the microbial ecology of the gut. Am JClin Nutr 1999;69:1052S-1057S.

Parraga ME, Spier SJ, Thurmond M et al: A clinical trial ofprobiotic administration for prevention of Salmonella shedding inthe postoperative period in horses with colic. J Vet Intern Med1997;11:36-41.

Weese JS: Microbiologic evaluation of commercial probiotics.J Am Vet Med Assoc 2002;220:794-797.

CALL FOR PAPERS

The Journal of Equine Veterinary ScienceThe Journal of Equine Veterinary Science (JEVS) extends an invitation to everyone involved in equine research to submit amanuscript describing their studies. We are especially interested in papers that contain new information of special interest toequine practitioners. JEVS has been publishing quality equine research papers for the past 21 years.

Download a copy of our author’s guidelines at www.j-evs.com. We also welcome nonreviewed, comprehensive reviews ofa topic of interest to equine practitioners. Our Viewpoint section is an ideal place to present an idea or news of your recent findingsin a nonreviewed format, with the purpose of generating dialogue.

William E. Jones, DVM, PhDEditorWej@j-evs.com

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