S. boulardii CNCM I-745 addresses the causes and symptoms of diarrhea with specific proven mechanisms of action

Saccharomyces boulardii CNCM I-745 addresses the causes and symptoms of diarrhea through multiple strain-specific mechanisms of action¹. Either it acts directly within the intestinal lumen (luminal action), indirectly to influence enzyme production (trophic action), or by affecting the mucosa including anti-inflammatory activity (mucosal action).²

In pre-clinical investigations in animal models or models of intestinal epithelial cells, S. boulardii CNCM I-745 has been demonstrated to counteract harmful bacterial toxins by blocking receptor sites, directly binding the toxin, or producing proteins that destroy them.³

For example, one protein produced by S. boulardii CNCM I-745 inhibits the cAMP-induced increase in chloride production that are caused by Cholera Toxin, which leads to increased water secretion. The toxin can also be directly bound by S. boulardii CNCM I-745 to prevent it damaging cells.³

Another anti-toxin protein is a secreted protease that degrades Clostridium difficile toxins A and B and the corresponding receptors.³

Finally, pre-clinical animal studies have reported that S. boulardii CNCM I-745 produces a protein phosphatase that dephosphorylates Escherichia coli lipopolysaccharide, reducing inflammation.³

Besides counteracting the harmful toxins produced by pathogenic bacteria, S. boulardii CNCM I-745 also prevents their invasion of gut cells by acting as a barrier, and by preserving tight junctions.³ The yeast inhibits phosphorylation of the myosin light chain (involved in forming tight junctions), preventing increased intestinal permeability.³ It has been demonstrated that this prevents access of bacteria such as Shigella.³

In vitro scanning and microscopy studies have demonstrated that S. boulardii CNCM I-745 can bind to bacterial strains such as E. coli, S. typhimurium to prevent adhesion to gut cells.³  In vivo imaging studies showed that S. boulardii CNCM I-745 can also enhance the duration of bacterial elimination through the digestive tract.³ It has also been reported that S. boulardii CNCM I-745 can directly inhibit the growth of bacteria such as Yersinia enterocolitium.²

The indirect trophic effects of Saccharomyces boulardii CNCM I-745

Pre-clinical studies have demonstrated that S. boulardii CNCM I-745 increases intestinal enzymatic activity.² It has been reported that S. boulardii CNCM I-745 administration is associated with an increase in:

• lactase, α-glucosidase and alkaline phosphatase that are involved in normal gut activity¹ ;
• polyamine production, substances involved in enterocyte maturation^1,2 ;
• disaccharidase that increases sugar digestion¹, that can counteract the sugar malabsorption and subsequent osmotic diarrhea induced by rotavirus⁴ ;
• enhanced absorption of D-glucose coupled to Na⁺ and the expression of the sodium-glucose cotransporter-1 (SGLT-1) which are involved in glucose transport into cells.⁵

S. boulardii CNCM I-745 also indirectly increases proteolysis of small N-terminal peptides by producing a leucine aminopeptidase belonging to the zinc-metalloprotease family, which counteracts reduced nutrient digestion.⁶

Another trophic action is immune action, where S. boulardii CNCM I-745 has the ability to enhance host responses to the presence of pathogenic bacteria via the stimulation of secreted immunoglobulin A (sIgA). For example in mice, the administration of S. boulardii CNCM I-745 increases the levels of circulating anti-C. difficile-toxin A IgA that bind and neutralise the toxin.³

Besides acting as a physical barrier, the intestinal mucosa is a repository for pro-inflammatory compounds.¹ S. boulardii CNCM I-745 acts on the intestinal mucosa to decrease the synthesis of pro-inflammatory cytokines It produces a small anti-inflammatory factor (Saccharomyces anti-inflammatory factor; butyrate, both linked to inhibition of mitogen-activated protein kinases (MAPK)  and NF-κB activity.¹ This inhibition results in decreased expression of inflammatory cytokines such IL-8 , IFN-ϒ, TNF-α and IL-6.¹

The administration of S. boulardii CNCM I-745 has been associated with an increase in short-chain fatty acids (SCFA), in particular butyrate and propionate.³ These compounds play a role in normal colonic function, including fluid absorption.³

Through its multiple mechanisms of action, S, boulardii CNCM I-745 creates a favourable growth environment for normal microbiota.⁷ Studies assessing fecal composition have shown that during dysbiosis, when there is a disturbance to the balance of gut microbiota, normal composition and diversity are restored rapidly upon administration of S. boulardii CNCM I-745 while overgrown species are reduced.⁷ However, in healthy individuals, S. boulardii CNCM I-745 does not affect gut microbiota composition nor diversity.²