Abstract
Saccharomyces boulardii CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated Clostridium difficile (C. difficile) infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of C. difficile. The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial C. difficile infection.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01473368.
Highlights
The human gut microbiota is a balanced and complex ecosystem, which exerts several physiological functions useful for the host, such as energy storage, digestion, maturation of the immune system and protection against colonization by pathogens (Zoetendal et al, 2006; Neish, 2009; Fujimura et al, 2010; Buffie and Pamer, 2013)
Group 1 was treated with Saccharomyces boulardii CNCM I-745 (SB) CNCM I-745 for 14 days; group 2 received AC for 7 days; group 3 was treated with SB for 14 days + AC for 7 days; group 4 received no treatment
Regarding the total fecal bile acids (BA) concentration, no significant change from baseline was observed at any time point, except for a single increase on day 13 in group 3, which had returned to baseline by day 21 (Figure 1)
Summary
The human gut microbiota is a balanced and complex ecosystem, which exerts several physiological functions useful for the host, such as energy storage, digestion, maturation of the immune system and protection against colonization by pathogens (Zoetendal et al, 2006; Neish, 2009; Fujimura et al, 2010; Buffie and Pamer, 2013). They promote the absorption of lipids by forming micelles containing dietary fat, before being reabsorbed in the terminal ileum and return to the liver via the portal circulation, forming an enterohepatic cycle During their passage through the intestinal lumen, the bile acids undergo consecutive metabolic steps performed by the microbiota, including (1) a separation of the amino acids from the sterol nucleus (deconjugation), and (2) the removal of the hydroxyl group on the carbon seven of the sterol nucleus (7-alpha-dehydroxylation).(Hofmann, 1999) In human intestinal disease, dysbiosis has been associated with alteration of both conjugation and transformation of BA (Duboc et al, 2013)
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