Background Enterotoxigenic Escherichia coli (ETEC) substantially contributes to the burden of diarrheal illnesses in developing countries. With the use of complementary in vitro models of the human digestive environment, TNO gastrointestinal model (TIM-1), and Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we provided the first detailed report on the spatial-temporal modulation of ETEC H10407 survival, virulence, and its interplay with gut microbiota. These systems integrate the main physicochemical parameters of the human upper digestion (TIM-1) and simulate the ileum vs ascending colon microbial communities and luminal vs mucosal microenvironments, captured from six fecal donors (M-SHIME). Results A loss of ETEC viability was noticed upon gastric digestion, while a growth renewal was found at the end of jejunal and ileal digestion. The remarkable ETEC mucosal attachment helped to maintain luminal concentrations above 6 log10 mL−1 in the ileum and ascending colon up to 5 days post-infection. Seven ETEC virulence genes were monitored. Most of them were switched on in the stomach and switched off in the TIM-1 ileal effluents and in a late post-infectious stage in the M-SHIME ascending colon. No heat-labile enterotoxin production was measured in the stomach in contrast to the ileum and ascending colon. Using 16S rRNA gene-based amplicon sequencing, ETEC infection modulated the microbial community structure of the ileum mucus and ascending colon lumen. Conclusions This study provides a better understanding of the interplay between ETEC and gastrointestinal cues and may serve to complete knowledge on ETEC pathogenesis and inspire novel prophylactic strategies for diarrheal diseases.

Differences in digestive physicochemical parameters may partially explain why children are more susceptible to EHEC infection than adults. Such data are essential for a full understanding of EHEC pathogenesis and would help in designing novel therapeutic approaches.

Enterotoxigenic Escherichia coli (ETEC) are major food-borne pathogens responsible for traveler's diarrhea. The production of adhesins and the secretion of enterotoxins constitute the major virulence traits of the bacteria. Treatments are mainly symptomatic and can involve antibiotherapy. However, given the rise of antibiotic resistance worldwide, there is an urgent need for the development of new preventive strategies for the control of ETEC infections. Among them, a promising approach is the use of probiotics. The aim of this study was to investigate, using complementary in vitro and in vivo approaches, the inhibitory potential of the yeast Saccharomyces cerevisiae CNCM I-3856 against the human ETEC reference strain H10407. In conventional culture media, S. cerevisiae significantly reduced ETEC growth and toxin production. The yeast also inhibited bacterial adhesion to mucin-agar and intestinal Caco-2/TC7 cells in a dose-dependent manner. Lastly, pre-treatment with S. cerevisiae inhibited interleukin-8 production by ETEC-infected intestinal cells. In streptomycin-treated mice, the probiotic yeast decreased bacterial colonization, mainly in the ileum, the main site of ETEC pathogenesis. For the first time, this study shows that the probiotic yeast S. cerevisiae CNCM I-3856 can exert an anti-infectious activity against a human ETEC strain through a multi-targeted approach, including inhibition of bacterial growth and toxin production, reduction of bacterial adhesion to mucins and intestinal epithelial cells, and suppression of ETEC-induced inflammation. Interestingly, the highest activity was obtained with a prophylactic treatment. Further studies will aim to assess the effect of the yeast on ETEC survival and virulence under human simulated digestive conditions.

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Enterotoxigenic Escherichia coli (ETEC) are a major cause of traveler's diarrhea and infant mortality in developing countries. Given the rise of antibiotic resistance worldwide, there is an urgent need for the development of new preventive strategies. Among them, a promising approach is the use of probiotics. Although many studies, mostly performed under piglet digestive conditions, have shown the beneficial effects of probiotics on ETEC by interfering with their survival, virulence or adhesion to mucosa, underlying mechanisms remain unclear. This review describes ETEC pathogenesis, its modulation by human gastrointestinal cues as well as novel preventive strategies with a particular emphasis on probiotics. The potential of in vitro models simulating human digestion in elucidating probiotic mode of action will be discussed.

Enterotoxigenic Escherichia coli (ETEC) and Enterohemorrhagic Escherichia coli (EHEC) are major food-and water-borne pathogens that constitute a serious public health threat in low-income and developed countries, respectively. Survival and expression of virulence genes in the human digestive tract are key features in bacterial pathogenesis, but the mechanisms behind these processes remain largely unknown due to obvious prohibition of human studies. Use of well-controlled and multi-parametric in vitro models can aid in addressing knowledge gaps in ETEC and EHEC pathogenesis. After a general description of the physiopathology of ETEC and EHEC infections, this chapter will give an overview of all the in vitro studies that have investigated the effect of the main physicochemical and biotic parameters of the human gut on pathogen survival and expression of virulence factors. We bring a picture of how ETEC and EHEC are able to adapt to each of the successive environments of the human gastrointestinal tract by reading many cues provided by both the host and the gut microbiota.

Enterotoxigenic Escherichia coli (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 Saccharomyces cerevisiae 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 Bifidobacterium and Lactobacillus 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 S. cerevisiae CNCM I-3856 against ETEC in the overall simulated human digestive tract, regardless of the inherent variability across individuals in the M-SHIME.

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