A Scientific Review of Pet Probiotics

SACCHAROMYCES BOULARDII "WHITE PAPER"

TAKE HOME MESSAGE:

•  Saccharomyces cerevisiae boulardii (S. boulardii) is a safe yeast-based probiotic for dogs and cats.
  
  
• S. boulardii prevents and treats antibiotic-associated diarrhea, Clostridium difficile infection, non-specific diarrhea, and inflammatory bowel disease.
  
  
• It's mechanism of action has been defined through many controlled studies and randomized clinical trials in humans, livestock, and companion animals.
  
  
• S. boulardii is the most extensively researched probiotic in peer-reviewed journals for various forms of gastrointestinal disturbances. 
  
  

What are probiotics?

Probiotics are live microorganisms that provide a positive effect on the gut microbiome and immune response to prevent and treat gastrointestinal disturbances.

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 supplementation for both humans and animals, regardless of physical condition.  

Probiotic organisms include various strains of bacteria and yeast. Strains of Lactobacilli, Streptococcus, and Bifidobacterium are the most commonly supplemented probiotic bacterial strains and have a long history of proclaimed probiotic effect.  

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 in both humans and animals. 

The hostile environment of the gastrointestinal tract-- low pH, bile salts, and digestive enzymes—does not make it easy on probiotics.

High quality pet probiotics must be able to withstand the gastrointestinal environment to reach the large intestine, the primary target for probiotic supplementation.

Human health and animal feed industries recognize the benefits of probiotics, and in recent years, the mechanism of action of many popular probiotic strains have been well-defined.

All commonly supplemented probiotic strains are safe, aid in nutrient digestibility, detoxify pathogens, and protect the gastrointestinal lining using various mechanisms of action.  

With regard to companion animals, research has focused primarily on the benefits of S. boulardii during gastrointestinal disturbances. 

What is Saccharomyces boulardii?

S. 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 humans and multiple animal species.boulardii favors temperatures at or near 37°C (98.6°F) which is necessary for survival in the GI tract of companion animals whose internal temperatures range from 37.5-39°C (99.5°-102.5°F; Fietto et al., 2004).

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 probiotic supplement for dogs and cats.

 Because yeast strains of probiotics are not native to the gastrointestinal tract, 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 pet diet and supplements

S. boulardii improves nutrient digestibility in pigs, horses, chickens, and cattle by directly improving fiber digestibility. This results in the production of volatile fatty acids (VFAs) which include, acetate, propionate, and butyrate.  Specifically, S. boulardii increases the ratio of butyrate production, a known gastrointestinal anti-inflammatory, and also improves energy utilization (Schneider et al., 2005).

Second, S. boulardii enhances brush border enzymes: enzymes produced in the enterocyte, the building block of the small intestine, which aid in the digestion of small saccharides and peptides. While the mechanism 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 and absorption and assists in maintaining cell integrity in the small intestine (More and Vandeplas, 2018).

2)    Antibiotic-Associated Diarrhea: How to treat diarrhea in dogs and cats

Antibiotic-associated diarrhea results when broad-spectrum antibiotics are administered orally or intravenously resulting in disruptions to the gut microbiome and is common in humans, dogs, cats, and horses. (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. 

S. boulardii has been shown to inhibit the overgrowth of pathogenic 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 (Szajewska and Kolodziej, 2015). 

Specifically related to supplementation in dogs, a symbiotic mixture of S. boulardii and other bacterial probiotic strains improved feed intake during antibiotic treatment and reduced the incidence of antibiotic-associated diarrhea (Whittemore et al., 2019). 

S. 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: Can Saccharomyces boulardii prevent/treat C. Diff?

The most common enteric pathogens in dogs and cats include C. difficile, E. coli, and Salmonella.  Bad bacteria thrive when the normal microflora and cells of the GI 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. 

C.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 et al., 2019).  In fact, C. difficile infection can be prevented in animals supplemented with S. boulardii (Pothoulakis et al., 1993)

E. coli primarily damages the gastrointestinal 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.  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 until the animal becomes immunocompromised either through physiological stress, disease, or other stressors including dietary changes, 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 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 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 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. 

 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 gastrointestinal 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.  

 6)    Non-Specific Acute Diarrhea: Impact of S. boulardii

During conditions of diarrhea which have no known cause, S. boulardii reduces the severity and risk of prolonged diarrhea (>7 days) in children and horses.  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. 

Is the yeast based probiotic S. boulardii the best for my pet?

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 dogs and cats to prevent pathogen invasion or loss of gastrointestinal homeostasis. 

Maintenance of healthy gastrointestinal function is necessary for the health and well-being of companion animals. A regular regimen of S. boulardii-containing probiotics not only has health benefits, but economic benefits by reducing the incidence of gastrointestinal disturbances which require medical intervention (Vermeersch et al., 2018).  

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. 

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.. 1998. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea. Dig. Dis. 16(5):292-307. doi: 10.1159/000016879. 

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.. 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.

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.

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. 

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. 

Whittemore, J. C., T. D. Moyers, and J. M. Price. 2019. Randomized, controlled, crossover trial of prevention of antibiotic-induced gastrointestinal signs using a symbiotic mixture in healthy research dogs. J. Vet. Intern. Med. 33(4):1619-1626. doi: 10.1111/jvim.15553.

To read the older version of "A REVIEW OF THE YEAST PROBIOTIC SACCHAROMYCES BOULARDII FOR DOGS AND CATS" click here...