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Basics

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BASICS

Definition!!navigator!!

In 1908 Elie Metchnikoff, a Russian researcher, studied the longevity of Bulgarians. He attributed their longevity and health to consumption of large amounts of bacterially fermented milk. The bacterium responsible for milk fermentation was given the name Bacillus bulgaricus and he defined this “probiotic” as “live microorganisms, which exhibit a health promoting effect.” The World Health Organization modified this initial definition in 2008 to “[l]ive microorganisms which when administered in adequate amounts confer a health benefit on the host.”

Bacterial Strains Used!!navigator!!

Potential probiotic strains should be able to survive the gastric environment, have antimicrobial properties, adhere to mucus and epithelial cells, and have properties to withstand the rigors of production. Both bacteria and yeast are used as microbial feed additives; the most common are Saccharomyces (yeast), Lactobacillus, Escherichia coli, Enterococcus, Bacillus, Streptococcus, and Bifidobacterium. These were initially selected based on knowledge from human medicine, as lactobacilli and bifidobacteria are particularly abundant in the human small intestine. Recent advances in knowledge of the microbiome have shown that the main species associated with GI health in horses are from the families Lachnospiraceae and Ruminococcaceae, of the order Clostridiales, which none of the above-described species belong to.

Survival In The Gi Tract!!navigator!!

Colonization is superior to mere survival in the GI tract, as probiotics can act longer beyond the period of administration. Generally, host-specific strains are believed to be able to colonize the GI tract of the indigenous host for longer periods of time. Probiotic strains can be recovered from feces of adults for 1 week. In foals fecal recovery tends to be longer, up to 3 weeks.

Mechanisms of Action!!navigator!!

There are 3 main mechanisms of action by which probiotics prevent colonization of the digestive tract by pathogenic strains or prevent disease:

  • Modulation of the host innate and acquired immune system—the immune system constantly samples the antigens present in the GI lumen and reacts with local and systemic modifications to the immune system
  • Antimicrobial action—some probiotics produce metabolites that are active against pathogenic bacteria and their toxins
  • Competitive exclusion, also termed colonization resistance—probiotics compete with pathogens for nutrients and take up ecologic niches to prevent proliferation of pathogenic bacteria

Many reported mechanisms of action of probiotics are based on in vitro studies only, and extrapolation of these results to in vivo conditions is controversial. Some evidence also has been generated by in vivo studies performed in laboratory animals or humans.

Regulation and Quality Control!!navigator!!

In North America probiotics can be classified as dietary or feed supplements “generally regarded as safe” (GRAS). They do not need to go through the process of drug approval. The US Food and Drug Administration only requires that supplements be labeled in a truthful and not misleading manner; however, even this rule is not rigorously enforced. For example, probiotics are not allowed to contain the claim “health promoting” on the label, but many products with such a claim are on the market.

Manufacturers of over-the-counter products in North America have no obligation to perform quality control of their products. Consequently, in North America, there are numerous probiotic products for use in horses that can be obtained over the counter, and claim to benefit the horse in various ways. Studies have shown that quality control of the contents of probiotics is poor. Only 2/13 (15%) of veterinary and human probiotics contained the specified organism concentration indicated on the product label. Some were missing organisms entirely or contained too little or too much of an active ingredient. Actual bacterial concentrations ranged from 0% to 215% of claimed amounts. All veterinary products contained <2% of the listed concentrations. Additionally, peer-reviewed published studies proving the efficacy of these products are limited, and in most cases lacking. Based on these limitations currently the use of over-the-counter commercial probiotics cannot be recommended for research or in a clinical setting.

In Europe probiotics are marketed as feed additives and are regulated by the EU. Since 2010 new probiotic supplements can only be marketed if they adhere to EU legislation 1831/2003. Products are licensed for a specific species, indication, and for a maximum duration of 10 years. There are currently only 4 products for horses on the market.

Evidence For Use!!navigator!!

The scope of the current literature about equine probiotics use has focused mainly on GI disease application. Although some studies have shown beneficial effects of probiotics, other studies could not corroborate these results. Overall, few studies are available, and these cannot be compared easily because of differences in study design and formulations used.

Therapy for Acute Colitis

The results from 2 available studies are equivocal. In 1 study there was no beneficial effect of probiotic administration. In the second study probiotic-treated horses had a shorter duration of diarrhea; however, there was no effect on survival or duration of stay in the clinic. Both studies had low case numbers, making the results questionable.

Prevention of Neonatal Diarrhea

There is currently not enough evidence that probiotics had a beneficial effect on prevention of neonatal foal diarrhea from the 4 available studies—2 studies showed a potentially harmful effect on the foals, with increasing incidence of severe diarrhea, while 1 study showed no effect and only 1 study reported a decrease in incidence of neonatal foal diarrhea.

Salmonella Shedding

The effect of probiotic administration on fecal Salmonella shedding is questionable. Of the 3 available studies only 1 study showed a reduction in Salmonella shedding, albeit not significant.

Sand Clearance

Probiotics have also been studied as an adjunct therapy for sand excretion. In the only available study sand excretion was increased when administering a product containing psyllium and a probiotic. It is, however, unclear if this effect was due to the psyllium or the probiotic.

Effect on the Microbiota

In humans and other animals probiotic administration has been shown to have an effect on the composition and structure of the microbiota. In horses this has only been studied in foals and an effect could not be shown.

As commercial probiotics were used in some studies, the results of these should be considered with caution owing to the lack of quality control of the products. Consequently, the current overall evidence is weak.

Safety and Side Effects!!navigator!!

Adverse effects of probiotic administration are rare. In adult horses, there are no published reports of enteric disease after probiotic administration. Even administration of up to 3 times the manufacturer's recommended dose to 18 healthy horses did not result in any adverse effects. Some adverse effects not related to enteric disease have been reported—1 of the horses developed hives after administration of the probiotic; however other factors could also have been responsible for these signs. The effect of probiotics in foals is likely to be different from that in adult horses owing to major difference in GI microbiota composition; 2 clinical field trials have reported an increased incidence of severe diarrhea in foals when treated with different probiotics.

Recommendations!!navigator!!

At this stage the use of commercial over-the-counter probiotics cannot be recommended. Currently there is no clear evidence that probiotics have beneficial effects but they actually might cause harm, particularly in foals, and potential side effects should always be considered.

Future Perspectives!!navigator!!

The GI microbiota of humans and animals consists of thousands of microbial species. All existing probiotics contain 1 or a few strains of bacteria, constituting only a very minor component of the total intestinal microbiota. Therefore, they might have limited ability to influence an individual's microbiota. Fecal microbial transplantation, the transfer of all microorganisms from a healthy donor to a diseased recipient, could be the future of probiotic research. Alternatively, selection of bacterial strain based on the current knowledge of the microbiota could be tried. Several bacteria now known to be associated with GI health could be selected and manufactured into a probiotic product.

Treatment

TREATMENT

Client Education

Clients often know superficially about probiotics and consider them a “natural treatment.” Clients should be made aware that there are no regulations or safety standards behind commercial probiotics and that some harm has been shown in administration of probiotics to foals. They should also be educated about the current lack of evidence of effect.

Miscellaneous

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MISCELLANEOUS

Abbreviations!!navigator!!

  • EU = European Union
  • GI = gastrointestinal

Internet Resources!!navigator!!

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Suggested Reading

Schoster AS, Weese JS, Guardabassi LG. Probiotic use in horses—what is the evidence for their clinical efficacy. J Vet Intern Med 2014;28:16401652.

Schoster AS, Staempfli HR, Abrahams M, et al. Effect of a probiotic on prevention of diarrhea and Clostridium difficile and Clostridium perfringens shedding in foals. J Vet Intern Med 2015;29:925931.

Weese JS, Martin H. Assessment of commercial probiotic bacterial contents and label accuracy. Can Vet J 2011;52:4346.

Author(s)

Author: Angelika Schoster

Consulting Editors: Henry Stämpfli and Olimpo Oliver-Espinosa