No abstract

Dietary fibers have well-known beneficial effects on human health, but their anti-infectious properties against human enteric pathogens have been poorly investigated. Enterotoxigenic Escherichia coli (ETEC) is the main agent of travelers’ diarrhea, against which targeted preventive strategies are currently lacking. ETEC pathogenesis relies on multiple virulence factors allowing interactions with the intestinal mucosal layer and toxins triggering the onset of diarrheal symptoms. Here, we used complementary in vitro assays to study the antagonistic properties of eight fiber-containing products from cereals, legumes or microbes against the prototypical human ETEC strain H10407. Inhibitory effects of these products on the pathogen were tested through growth, toxin production and mucus/cell adhesion inhibition assays. None of the tested compounds inhibited ETEC strain H10407 growth, while lentil extract was able to decrease heat labile toxin (LT) concentration in culture media. Lentil extract and specific yeast cell walls also interfered with ETEC strain H10407 adhesion to mucin beads and human intestinal cells. These results constitute a first step in the use of dietary fibers as a nutritional strategy to prevent ETEC infection. Further work will be dedicated to the study of fiber/ETEC interactions within a complex gut microbial background.

The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler’s diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.