Multi-targeted properties of the probiotic <i>saccharomyces cerevisiae</i> CNCM I-3856 against enterotoxigenic <i>escherichia coli</i> (ETEC) H10407 pathogenesis across human gut models

Abstract

Enterotoxigenic <i>Escherichia coli</i> (ETEC) is one of the most common causes of acute traveler's diarrhea. Adhesins and enterotoxins constitute the major ETEC virulence traits. With the dramatic increase in antibiotic resistance, probiotics are considered a wholesome alternative to prevent or treat ETEC infections. Here, we examined the antimicrobial properties of the probiotic <i>Saccharomyces cerevisiae</i> CNCM I-3856 against ETEC H10407 pathogenesis upon co-administration in the TNO gastrointestinal Model (TIM-1), simulating the physicochemical and enzymatic conditions of the human upper digestive tract and preventive treatment in the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), integrating microbial populations of the ileum and ascending colon. Interindividual variability was assessed by separate M-SHIME experiments with microbiota from six human individuals. The probiotic did not affect ETEC survival along the digestive tract. However, ETEC pathogenicity was significantly reduced: enterotoxin encoding virulence genes were repressed, especially in the TIM-1 system, and a lower enterotoxin production was noted. M-SHIME experiments revealed that 18-days probiotic treatment stimulate the growth of <i>Bifidobacterium</i> and <i>Lactobacillus</i> in different gut regions (mucosal and luminal, ileum and ascending colon) while a stronger metabolic activity was noted in terms of short-chain fatty acids (acetate, propionate, and butyrate) and ethanol production. Moreover, the probiotic pre-treated microbiota displayed a higher robustness in composition following ETEC challenge compared to the control condition. We thus demonstrated the multi-inhibitory properties of the probiotic <i>S. cerevisiae</i> CNCM I-3856 against ETEC in the overall simulated human digestive tract, regardless of the inherent variability across individuals in the M-SHIME.