A Scientific Review of Equine Probiotics

SACCHAROMYCES BOULARDII "WHITE PAPER"

TAKE HOME MESSAGE:

  • Horses’ digestive tracts provide significant nutritional challenges which are important to factor into probiotic supplementation.
  • Saccharomyces cerevisiae boulardii (S. boulardii) is a safe yeast-based probiotic for horses.
  • S. boulardii is the most extensively researched probiotic in peer-reviewed journals for various forms of gastrointestinal disturbances. 

How does a horse’s digestive system work?

The equine digestive tract can be particularly challenging compared to other monogastric species.  Horses are considered non-ruminant herbivores or hindgut fermenters. Horses differ from other monogastrics (“one stomach”), such as humans, in that they are herbivores and designed to consistently graze. Fun fact: Horses are actually closest in digestive tract anatomy to a rabbit!

Being designed for constant consumption, horses also constantly produce stomach acid (HCl) and other gastric enzyme juices, versus humans or dogs who produce stomach acid in anticipation of a meal. The horse’s distinct physiology reminds us that current management practices of feeding meals 2-3 times per day is less than ideal for their digestive health. 

Additionally, the small intestine is significantly shorter than that of other monogastric animals, i.e. there is less time for starch, sugar, protein, and fat to be digested and absorbed. An excess of nutrients will not have adequate time in the small intestine to be digested and absorbed, so those nutrients will travel to the large intestine (the cecum and colon), where they will be fermented. Fermentation of feed that is not meant to be fermented increases the risk of microbiome disturbances, colic, disease, and overall inflammation. 

So how do we best manage our horses’ feeding program to promote digestive health? The keys are: 


1) Improving nutrient digestibility;

2) Protecting against microbiome shifts caused by changes in diet, stress, or pathogens.  


The most common and economical method for protecting against equine digestive problems is through dietary probiotic supplements

What are probiotics? 

Probiotics are live microorganisms that positively impact the gut microbiome to support normal gastrointestinal and immune function.  Any humans or animals that eat fermented food/feed products have been consuming naturally occurring probiotics for centuries.  Advances in processing techniques and technologies have improved probiotic production, maximizing the beneficial properties of using probiotics for horses.

Probiotic organisms include various strains of bacteria and yeast.  Strains of Lactobacilli, Streptococcus, and Bifidobacterium are the most commonly supplemented probiotic bacterial strains in horses and have mixed results regarding effectiveness.  

 In the last decade, a specific yeast strain of probiotic, Saccharomyces cerevisiae boulardii (S. boulardii), has received noteworthy attention as an effective supplement for enhancing digestive function and supporting intestinal immune response in horses.

 What is Saccharomyces boulardii?

  1. boulardii is a non-pathogenic anaerobic yeast strain first identified in 1920 by French microbiologist Henri Boulard while seeking a heat tolerant yeast for wine fermentation (McFarland, 2010).  Research into probiotic effects of S. boulardii began in 1982 and since, the benefits and mechanisms of action have been well-defined in human and various animal species.  
  2. boulardii favors temperatures at or near 37°C (98.7°F; Fietto et al., 2004) which is necessary for survival in the equine GI tract which has an  internal temperature ranging from 37.5-38.6° C (99.5-101.5°F).  Furthermore, this heat tolerance allows S. boulardii to withstand temperatures common in feed processing and supplement production.  Survivability during processing prior to supplementation is imperative to provide the best probiotics for horses. 

Because yeast strains of probiotics are not native to the gastrointestinal tract of any mammal, they must be continuously supplemented or they will be eliminated from the hindgut within 3-5 days of suspending supplementation (More and Swidsinski, 2015).  Consistent supplementation, however, results in rapid accumulation in the large intestine allowing for a quick response during times of trouble.  The mechanisms of action of S. boulardii are abundant and depend upon the specific gastrointestinal disturbance. 

Saccharomyces boulardii  Benefits

1)    Nutrient Digestibility: Impact on equine supplements and diet 

  1. boulardii improves nutrient digestibility in livestock species, including horses, by directly improving fiber digestibility in the hindgut. Fiber is the primary component of equine diets, and is the majority of the substrate used in hindgut fermenters.  Increased fiber digestibility results in the production of volatile fatty acids (VFAs) –acetate, propionate, and butyrate—which are the primary sources of energy to meet maintenance nutrient requirements in horses.  S. boulardii specifically results in an increase in butyrate, a known gastrointestinal anti-inflammatory, which also improves energy utilization (Schneider et al., 2005).  

Second, S. boulardii enhances brush border enzymes produced by enterocytes, the building block cells of the small intestine, and aids in the digestion of small saccharides and peptides.  While the specific mechanism by which S. boulardii enhances brush border enzymes is still unknown, S. boulardii is believed to play a major role in the up-regulation of polyamine synthesis.  Polyamines are necessary for cell proliferation and differentiation and enhance the expression of intestinal enzymes and membranous nutrient transporters.  

Bottom line: S. boulardii improves nutrient digestibility in the foregut and hindgut, and assists in maintaining cell integrity in the small intestine (More and Vandeplas, 2018). 

2)    Antibiotic-Associated Diarrhea: What can I give my horse to stop diarrhea?

Antibiotic-associated diarrhea can occur from use of broad-spectrum antibiotics, administered orally or intravenously, which results in disruptions to the gut microbiome.  (McFarland, 2008).  Broad-spectrum antibiotics are not specific to the bacteria responsible for infection; perhaps the largest side effect of antibiotics is the destruction of beneficial bacteria in the gut.  These shifts and disturbances to the population and variety of microbes in the GI tract allows diarrhea-causing, opportunistic bacteria to thrive, resulting in antibiotic-associated diarrhea.

  1. boulardii has been shown to inhibit the overgrowth of bad bacteria during antibiotic treatment.  A meta-analysis in human medicine reported that supplementation of S. boulardii reduced the risk of antibiotic-associated diarrhea by up to 20% in adults (Szajwska and Kolodziej, 2015).  
  2. boulardii supplementation also improves rebound establishment of healthy microflora following the completion of antibiotic treatment without altering the effectiveness of common antibiotics (Swidsinski et al., 2008; Buts, 2009; More and Swidsinski, 2015; Selig et al., 2020). 

3)    Pathogen Blocking and Detoxification: C. diff and Salmonella in Horses

The most common enteric pathogens in horses include C. difficile, E. coli, and Salmonella.  Bad bacteria thrive when the normal bacterial ecosystem and cells of the horse digestive tract are damaged due to stress, disease, changes in diet, etc.  Pathogenic bacteria are considered opportunistic based on their ability to thrive when gastrointestinal homeostasis is lost.  Maintenance of healthy microflora and gastrointestinal health is necessary to prevent opportunistic pathogenic bacteria from creating more damage and leading to disease. 

  1. difficile infection is often associated with antibiotic-associated diarrhea and is the most studied with regard to S. boulardii supplementation.  Infection is stimulated by two toxins, toxin A and B.  S. boulardii prevents the C. difficile toxins from binding to cells in the GI tract, lyses the bacteria, and prevents excessive immune response (Czerucka and Rampal, 2019).  In fact, C. difficile infection can be prevented in animals supplemented with S. boulardii (Pothoulakis et al., 1993).  
  2. coli primarily damages the GI tract by breaking down the tight junctions which hold the cells of the gastrointestinal lining together.  The breakdown of tight junctions results in intestinal permeability and excessive stimulation of inflammatory pathways resulting in tissue damage.  This is commonly referred to as Leaky Gut Syndrome, a common topic of discussion in equine nutrition.  E. coli first adheres to the epithelial cells in the GI tract.  S. boulardii not only physically prevents E. coli contact with the intestinal lining but protects the integrity of tight junctions and modulates the inflammatory response (Stier and Bischoff, 2016; Czerucka and Rampal, 2019). 

Salmonella is abundant in the environment, but often does not become pathogenic to horses until they become immunocompromised either through physiological stress, disease, or other stressors including dietary change, etc. (Bradbery et al., 2015).  S. boulardii prevents invasion of Salmonella by inhibiting a specific molecular pathway called the Rac pathway (Martins et al., 2010).  Additionally, S. boulardii immobilizes Salmonella inhibiting their ability to invade the gastrointestinal epithelial cells resulting in Salmonella excretion. 

4)    Anti-inflammatory Effects: Probiotics and Inflammation

Inflammation is associated with the innate immune response and is not pathogen-specific, meaning that it is quickly activated as the immune system’s first response.  Inflammation is stimulated by pathogens or tissue damage and is regulated by inflammatory cells and cytokine-guided crosstalk.  S. boulardii modulates the innate immune response in horses by down-regulating pro-inflammatory cytokines including TNFa, interleukins, and prostaglandins by inhibiting various intracellular signaling molecules (NF-kB, MAP kinases; Pothoulakis, 2009; Ibanez et al., 2019).  

Inhibition of pro-inflammatory cytokines is paired with the up-regulation of anti-inflammatory factors (e.g. IL-10), mucins, and tight junctions which are responsible for protection and repair of damaged gastrointestinal epithelia (Rodriguez-Nogales et al., 2018).  Leaky Gut Syndrome is often associated with failure of tight junctions between cells of the gastrointestinal epithelial lining thus improved tight junctions and mucins can prevent and protect against pathologies associated with Leaky Gut Syndrome in horses.  

5)    Adaptive Immune Response: Probiotics and the Immune System

The adaptive immune system responds more slowly than the innate immune system, but with greater specificity.  B-cells of the adaptive immune system develop antibodies, or immunoglobulins (Ig), specific for various pathogens in order to mount a targeted response.  Immunoglobulin A (IgA) is the first antibody released in response to a pathogen in the GI tract (Stier and Bischoff, 2016).

Investigators discovered that supplementation with S. boulardii improves IgA and IgM production in healthy mature mice, weanling rats, and C. difficile infected mice (Stier and Bischoff, 2016). 

Data suggests that S. boulardii supplementation optimizes both the innate and adaptive immune systems to maintain gastrointestinal function, a healthy immune response, and protection against disease-causing pathogens in horses. 

6)    Non-Specific Acute Diarrhea: Probiotics for horses with diarrhea

Conditions of diarrhea with no known cause are quite common in horses.  S. boulardii reduces the severity and risk of prolonged diarrhea by as many as 7 days in horses (Desrochers et al., 2005).  The mechanism of action is unknown since the cause of diarrhea is unknown; however, S. boulardii likely protects from non-specific cases of diarrhea through one or a combination of the mechanisms of action described above.  

What is the best probiotic for horses?

Consistent supplementation with S. boulardii improves nutrient digestibility, optimizes the immune system response to pathogens, physically and biochemically protects against common gastrointestinal pathogens, reduces the risk of gastrointestinal disturbance, and protects against antibiotic-associated diarrhea.  These data gathered from a multitude of monogastric species suggest S. boulardii may be the best probiotic for horses to prevent pathogen invasion or loss of gastrointestinal homeostasis.  

Maintenance of healthy gastrointestinal function is necessary for the health and well-being of horses, particularly those undergoing frequent stress through intense performance careers, transportation stress, breeding, or diet changes.  A regular regimen of S. boulardii-containing probiotic not only has health benefits, but economic benefits by reducing the incidence of occasional gastrointestinal disturbances which require medical intervention (Vermeersch et al., 2018).  

FullBucket’s line of high-quality equine probiotics were designed with your horse’s digestive system in mind! Microencapsulated Saccharomyces boulardii is offered in all of our probiotics at the correct concentrations to support your horse’s gut health. 

 

REFERENCES

 Bradbery, A. N., J. A. Coverdale, L. M. Lucia, G. R. Acuff, and C. J. Hartz. 2015. Detection of Salmonella in equine facility environmental samples by 2 methods. J. Equine Vet. Sci. 35(5):431-432. doi: 10.1016/j.jevs.2015.03.125.


Buts, J. P.. 2009. Twenty-five years of research on Saccharomyces boulardii trophic effects: updates and perspectives. Dig. Dis. Sci. 54:15-18. doi: 10.1007/s10620-008-0322-y.


Czerucka, D., and P. Rampal. 2019. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. 


Desrochers, A. M., B. A. Dolente, M. F. Roy, R. Boston, S. Carlisle. 2005. Efficacy of Saccharomyces boulardii for treatment of horses with acute enterocolitis. J. Am. Vet. Med. Assoc. 227(6):954-959. doi: 10.2460/javma.2005.227.954.


Fietto, J. L. R., R. S. Araujo, F. N. Valadao, L. G. Fietto, R. L. Brandao, M. J. Neves, F. C. O. Gomes, J. R. Nicoli, and I. M. Castro. 2004. Molecular and physiological comparisons between Saccharomyces cerevisiae and Saccharomyces boulardii. Can. J. Microbiol. 50:615-621. doi: 10.1139/w04-050.


Ibanez, L., R. Pontier-Bres, F. Larbret, A. Rekima, V. Verhasselt, C. Blin-Wakkach, and D. Czerucka. 2019. Saccharomyces boulardii strain CNCM I-745 modifies the mononuclear phagocytes response in the small intestine of mice following Salmonella typhimurium infection. Front. Immunol. 10:643. doi: 10.3389/fimmu.2019.00643. 


Martins, F. S., G. Dalmasso, R. M. Aranes, A. Doye, E. Lemichez, P. Lagadec, V. Imbert, J. F. Peyron, P. Rampal, J. R. Nicoli, and D. Czerucka. 2010. Interaction of Saccharomyces boulardii with Salmonella enterica serovar typhimurium protects mice and modifies T84 cell response to the infection. PLoS One. 5:e8925. doi: 10.1371/journal.pone.0008925. 


McFarland, L. V. 2010. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J. Gastoenterol. 16(18):2202-2222. doi: 10.3745/wjg.v16.i18.2202.


More, M. I., and A. Swidsinski. 2015. Saccharomyces boulardii CNCM I-745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis – a review. Clin. Exp. Gastroenterol. 8:237-255. doi: 10.2147/CEG.S85574.


More, M. I., and Y. Vandenplas. 2018. Saccharomyces boulardii CNCM I-745 improves intestinal enzyme function: a trophic effects review. Clin. Med. Insights Gastroenterol. 11:1-14. doi: 10.1177/1179552217752679. 


Pothoulakis, C., C. P. Kelly, M. A. Joshi, N. Gao, C. J. O’Keane, I. Castagliuolo, and J. t. Lamont. 1993. Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum. Gastroenterol. 104:1108-1115. doi: 10.1016/0016-5085(93)90280-P.


Pothoulakis, C.. 2009. Review article: Anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment. Pharmacol. Ther. 30(8):826-833. doi: 10.1111/j.1365-2036.20009.04102.x.


Rodriguez-Nogales, A., F. Algieri, J. Garrido-Mesa, T. Vezza, M. P. Utrilla, N. Chueca, F. Garcia, M. E. Rodriguez-Cabezas, and J. Galvez. 2018. Intestinal anti-inflammatory effect of the probiotic Saccharomyces boulardii in DSS-induced colitis in mice: Impact on microRNAs expression and gut microbiota composition. J. Nutr. Biochem. 61:129-139. doi: 10.1016/j.jnutbio.2018.08.005. 


Schneider, S. M., F. Girard-Pipau, J. Filippi, X. Hebutrne, D. Moyse, G. C. Hinojosa, A. Pompei, and P. Rampal. 2005. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World J. Gastroenterol. 11(39):6165-6169. doi: 10.3748/wjg.v11.i39.6165.


Selig, D. J., J. P. Deluca, Q. Li, H. Lin, K. Nguyen, S. M. Scott, J. C. Susa, C. T. Vuong, L. H. Xie, and L. R. Livezey. 2020. Saccharomyces boulardii CNCM I-745 probiotic does not alter the pharmacokinetics of amoxicillin. Drug. Metab. Pers. Ther. 35(1). doi: 10.1515/dmpt-2019-0032.xml. 


Stier, H., and S. C. Bischoff. 2016. Influence of Saccharomyces boulardii CNCM I-745 on the gut-associated immune system. Clin. Exp. Gasatroenterol. 9:269-279. doi: 10.2147/CEG.S111003. 


Swindsinski, A., V. Loening-Baucke, H. Verstraelen, S. Osowska, and Y. Doerffel. 2008. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterol. 135:568-579. doi: 10.1053/j.gastro.2008.04.017.


Szajewska, H., and M. Kolodziej. 2015. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea. Aliment. Pharm. Ther. 42:793-801. doi: 10.1111/apt.13344. 


Vermeersch, S. J., Y. Vandenplas, A. Tanghe, M. Elseviers, and L. Annemans. 2018. Economic impact of S. boulardiiCNCM I-745 for prevention of antibiotic associated diarrhea in hospitalized patients. Acta. Gastroenterol Belg. 81(2):269-276. 

To read the original version, Saccharomyces Boulardii Probiotic White Paper for Horses, click here....



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