by Laura Brown, ND
Leaky Gut and the Importance of a Healthy Microbiome
In conditions that promote a leaky gut, the compounds of the food bolus that are usually kept safely in the intestinal lumina—including undigested food macromolecules, toxins, bacteria, or parts of bacteria known as endotoxins—has now the potential to pass through the fragile and unicellular mucosal membrane of the small intestine, and to reach the blood circulation. This can ultimately lead to body-wide tissue damage. This intestinal permeability can contribute to worsening of chronic diseases and quality of life in certain individuals who suffer from depression, kidney disease, cardiovascular disease, inflammatory bowel disease, irritable bowel syndrome, type 2 diabetes, obesity, and HIV infection. Auto-immune diseases have also been linked to leaky gut. Indeed, intestinal permeability appears to be a critical underlying condition to evaluate and treat in an integrative approach.
Much attention has been placed recently on the microbiome. The body of scientific knowledge is vast and large, and it is becoming established in science that the microbiome greatly influences disease outcome, treatment efficacy, tolerability of medications, and quality of life. It is great that we can now safely say that yes, our gut really does matter! So, what about the bacterial flora that make up our microbiota? I wanted to bring your attention to one particular strain of probiotics: Saccharomyces boulardii.
S. boulardii is not a bacterium per se, like Lactobacilli or Bifidobacterium, but a type of “good” yeast well known for its potential to prevent and treat antibiotic-associated or infectious diarrhea. S. boulardiialso shows evidence to prevent and treat leaky gut, and to reduce irritable bowel syndrome (IBS) symptoms (bloating, abdominal pain, and irregular bowel movement patterns). Further preclinical studies demonstrate the need for more research on the use of S. boulardii to help mitigate inflammation in bowel conditions like Crohn’s and colitis, Helicobacter pylori infections, candidiasis, dyslipidemia, and small intestine bacterial overgrowth.
How Does S. boulardii “Tighten the Gap” in a Leaky Gut?
S. boulardii is a probiotic yeast discovered in 1920 by a French biologist named Henri Boulard. When Boulard travelled to Indochina, he noticed that people who ingested a drink made from the skins of the lychee and mangosteen fruits were seemingly protected from diarrhea. How does this happen? That is where S. boulardiicomes into action with its antimicrobial properties and its capacity to support immune modulation, enzymatic activity, short-chain fatty-acid production, and gut barrier function.
Immune Modulation
S. boulardii contributes to a healthy microbiome and a stronger immunity by:
- supporting the modulation of an important immunoglobulin, secretory IgA in the intestinal lining, which is the first line of defense against pathogens in the intestine;
- increasing mucin, which creates a layer of protection, so pathogens have less of a chance to adhere and cause damage to the intestinal cells; and
- upregulating Kupffer cells in the liver as well as serum IgM which respectively filters harmful proteins and bacteria from the blood and provides first-line defence of systemic immunity.
In healthy individuals, S. boulardii is protective against inflammatory immune response of pathogenic (“traveller’s”) diarrhea. Stable to 37 °C, S. boulardii’s rugged cell-wall structure is thought to play a role in stimulating the immune system’s cytokines including interleukin (IL)‑1β, IL‑12, IL‑6, TNFα, as well as IL‑10. It also helps in the maturation of dendritic cells through the induction of CD80 and CD86. In animal studies, S. boulardii upregulates phosphatidylinositol 3‑kinase (PI3K), an important protein required for key functions of human cells, often observed to decline in oxidative, inflammatory, and cancerous conditions.
Enzymatic Support for the Gut Lining
The cells in the intestinal tract naturally turn over every three to five days, but this cycle is increased during infection or inflammation. The replacement of immature gut-lining cells lack healthy quantities of brush-border enzymes and transporters necessary for nutrient absorption. This can shift more hydration into the intestinal lumen, upregulating the diarrheal cycle. Also called trophic effects, the enzymatic activity of S. boulardii aids the immature enterocytes with increased enzymes to break down food and bacterial toxins. Thus, enzymatic production of S. boulardii can help limit the cycle of inflammatory bowel conditions, diarrhea, and leaky gut through preventative measures, ultimately leading to healing.
Short-chain Fatty Acid Production
S. boulardii is also considered as a prebiotic, thanks to its cell-wall components (glucans, mannoproteins, and chitin) which feed bacteria in the large intestine responsible for making short-chain fatty acids (SCFAs), mostly acetate, propionate, and butyrate. Numerous functions of SCFAs highlight their important impact on gut health and host metabolism. Especially, this is the mechanism by which S. boulardiiis thought to support the microbiota in a faster return to health after antibiotic therapy.
Antimicrobial Effects
Reduction in pathogenic damage will reduce the chance of a leaky gut and its downstream effects. S. boulardii is the first yeast to be used as a probiotic, and research supports its benefit as an adjunctive therapy in Helicobacter pylori infections; diarrhea from Clostridium difficile, Salmonella, Shigella, and Escherichia coli; rota viruses, candidiasis; and small intestinal bacterial overgrowth. How does it do it? S. boulardiibinds directly to pathogens, preventing them from adhering to the gut lining, and cleans up toxins released from invasive bacteria.
Gut-Barrier Function
S. boulardii maintains the integrity of the gap junctions between infected enterocytes; it prevents the activation of NF‑κB and MAP kinase pathways—that puts the brakes on IL‑8. It also regulates E‑cadherin recycling, a component on cell surfaces required for adhesion to one another. When it comes to Candida albicans, S. boulardiimay prevent it from growing filaments (a common penetrator into the gut lining), producing biofilms, and adhering to the gut lining.
Dosage and Duration
If you are not under the care of naturopathic doctor (ND), it is advised to follow the directions of use on the label of an approved product from Health Canada, which will carry a natural product number (NPN). Otherwise, an ND may suggest you take it longer or shorter depending on your condition such as gastritis, leaky gut, IBS, infectious gastroenteritis, or for traveler’s diarrhea. Research shows it achieves a therapeutic concentration in the colon within three days and is cleared within two to five days once stopped. Fungemia with S. boulardiiwas reported in one single case of an immune-compromised 79‑year‑old postoperative female.
Although S. boulardiiis stable through acidic conditions in the stomach, exposure to bile salts, and gastrointestinal enzymes, it is still recommended to choose enteric-coated capsules. Moreover, as opposed to most of the probiotic strains, it is stable at room temperature, so refrigeration is not necessary. However, if you have opened the product and will use it for a while, refrigeration is helpful to ensure optimum potency and delivery. Refrigeration is absolutely necessary if S. boulardiiis mixed with other strains that require refrigeration, such as most Lactobacillus and Bifidobacterium strains. S. boulardiiis a noncommensal yeast and, due to its fungal properties, it is naturally resistant to antibiotics; therefore, it has less chance of developing antimicrobial resistance and can be safely coadministered with antibiotics.
Conclusion
S. boulardii’s activity in the large and small intestines includes immune modulation, enzymatic activity, SCFA production, antimicrobial properties, and gut-barrier function. S. boulardiiis prescribed to treat both children and adult conditions of dysbiosis, and it shows general unspecific immune activation on the intestinal microbiota of healthy individuals. For the credibility listed above, it can be purposefully added to a regime that includes an enteric-coated, refrigerated Lactobacillus‑ or Bifidobacterium-based multistrain probiotic.
More on how to care for the gut in this author’s latest book: Beyond Digestion: How Gut Health Connects to Your Body, Mind and Soul.
References
- Terciolo, C., M. Dapoigny, and F. Andre. “Beneficial effects of Saccharomyces boulardii CNCM I‑745 on clinical disorders associated with intestinal barrier disruption.” Clinical and Experimental Gastroenterology, Vol. 12 (2019): 67–82.
- Ohlsson, L., A. Gustafsson, E. Lavant, K. Suneson, L. Brundin, Å. Westrin, L. Ljunggren, and D. Lindqvist. “Leaky gut biomarkers in depression and suicidal behavior.” Acta Psychiatrica Scandinavica, Vol. 139, No. 2 (2019): 185–193. Erratum in: [No authors listed.] “Corrigendum.” Acta Psychiatrica Scandinavica, Vol. 142, No. 5 (2020): 423.
- Lau, W.L., and N.D. Vaziri. “The leaky gut and altered microbiome in chronic kidney disease.” Journal of Renal Nutrition, Vol. 27, No. 6 (2017): 458–461.
- Meijers, B., F. Jouret, and P. Evenepoel. “Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease.” Pharmacological Research, Vol. 133 (2018): 101–107.
- Terciolo, C., M. Dapoigny, and F. Andre. “Beneficial effects of Saccharomyces boulardii.”
- Mu, Q., J. Kirby, C.M. Reilly, and X.M. Luo. “Leaky gut as a danger signal for autoimmune diseases.” Frontiers in Immunology, Vol. 8 (2017): 598.
- Czerucka, D., and P. Rampal. “Diversity of Saccharomyces boulardii CNCM I‑745 mechanisms of action against intestinal infections.” World Journal of Gastroenterology, Vol. 25, No. 18 (2019): 2188–2203.
- Pineton de Chambrun, G., C. Neut, A. Chau, M. Cazaubiel, F. Pelerin, P. Justen, and P. Desreumaux. “A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome.” Digestive and Liver Disease, Vol. 47, No. 2 (2015): 119–124.
- Kaźmierczak-Siedlecka, K., J. Ruszkowski, M. Fic, M. Folwarski, and W. Makarewicz. “Saccharomyces boulardii CNCM I‑745: A non-bacterial microorganism used as probiotic agent in supporting treatment of selected diseases.” Current Microbiology, Vol. 77, No. 9 (2020): 1987–1996.
- Czerucka, D., and P. Rampal. “Diversity of Saccharomyces boulardii CNCM I‑745.”
- Qamar, A., S. Aboudola, M. Warny, P. Michetti, C. Pothoulakis, J.T. LaMont, and C.P. Kelly. “Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice.” Infection and Immunity, Vol. 69, No. 4 (2001): 2762–2765.
- Gogineni, V.K., L.E. Morrow, and M.A. Malesker. “Probiotics: Mechanisms of action and clinical applications.” Journal of Probiotics & Health, Vol. 1, No. 1 (2013): Article #2, 11 p.
- Stier, H., and S.C. Bischoff. “Influence of Saccharomyces boulardii CNCM I‑745 on the gut-associated immune system.” Clinical and Experimental Gastroenterology, Vol. 9 (2016): 269–279.
- Smith, I.M., J.E. Christensen, N. Arneborg, and L. Jespersen. “Yeast modulation of human dendritic cell cytokine secretion: An in vitro study.” PLoS One, Vol. 9, No. 5 (2014): e96595.
- Liu, B., X. Piao, W. Niu, Q. Zhang, C. Ma, T. Wu, Q. Gu, T. Cui, and S. Li. Kuijieyuan. “Decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4‑dependent PI3K/AKT/NF‑κB oxidative and inflammatory signaling and gut microbiota.” Frontiers in Pharmacology, Vol. 11 (2020): 1036.
- Buts, J.P., and N. De Keyser. “Transduction pathways regulating the trophic effects of Saccharomyces boulardii in rat intestinal mucosa.” Scandinavian Journal of Gastroenterology, Vol. 45, No. 2 (2010): 175–185.
- Corinaldesi, R., V. Stanghellini, G. Barbara, P. Tomassetti, and R. De Giorgio. “Clinical approach to diarrhea.” Internal and Emergency Medicine, Vol. 7, Suppl. 3 (2012): S255–S262.
- Moré, M.I., and Y. Vandenplas. “Saccharomyces boulardii CNCM I‑745 improves intestinal enzyme function: A trophic effects review.” Clinical Medicine Insights. Gastroenterology. Vol. 11 (2018): 1179552217752679.
- Swidsinski, A., V. Loening-Baucke, S. Schulz, J. Manowsky, H. Verstraelen, and S. Swidsinski. “Functional anatomy of the colonic bioreactor: Impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders.” Systematic and Applied Microbiology, Vol. 39, No. 1 (2016): 67–75.
- Czerucka, D., and P. Rampal. “Diversity of Saccharomyces boulardii CNCM I‑745.”
- Kaźmierczak-Siedlecka, K., J. Ruszkowski, M. Fic, M. Folwarski, and W. Makarewicz. “Saccharomyces boulardii CNCM I‑745.”
- Edwards-Ingram, L., P. Gitsham, N. Burton, G. Warhurst, I. Clarke, D. Hoyle, S.G. Oliver, and L. Stateva. “Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae.” Applied and Environmental Microbiology, Vol. 73, No. 8 (2007): 2458–2467.
- Mumy, K.L., X. Chen, C.P. Kelly, and B.A. McCormick. “Saccharomyces boulardii interferes with Shigella pathogenesis by post invasion signaling events.” American Journal of Physiology. Gastrointestinal and Liver Physiology, Vol. 294, No. 3 (2008): G599–G609.
- Gedek, B.R. “Adherence of Escherichia coli serogroup O 157 and the Salmonella typhimurium mutant DT 104 to the surface of Saccharomyces boulardii.” Mycoses. Vol. 42, No. 4 (1999): 261–264.
- Krasowska, A., A. Murzyn, A. Dyjankiewicz, M. Łukaszewicz, and D. Dziadkowiec. “The antagonistic effect of Saccharomyces boulardii on Candida albicans filamentation, adhesion and biofilm formation.” FEMS Yeast Research, Vol. 9, No. 8 (2009): 1312–1321.
- Moré, M.I., A. Swidsinski. “Saccharomyces boulardii CNCM I‑745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis – a review.” Clinical and Experimental Gastroenterology, Vol. 8 (2015): 237–255.
- Thygesen, J.B., H. Glerup, and B. Tarp. “Saccharomyces boulardii fungemia caused by treatment with a probioticum.” BMJ Case Reports, Vol. 2012 (2012): bcr0620114412.
- Edwards-Ingram, L., P. Gitsham, N. Burton, G. Warhurst, I. Clarke, D. Hoyle, S.G. Oliver, and L. Stateva. “Genotypic and physiological characterization of Saccharomyces boulardii.”
- Kaźmierczak-Siedlecka, K., J. Ruszkowski, M. Fic, M. Folwarski, and W. Makarewicz. “Saccharomyces boulardii CNCM I‑745.” Moré, M.I., and A. Swidsinski. “Saccharomyces boulardii CNCM I‑745.”