Spatial and temporal modulation of enterotoxigenic E. coli H10407 pathogenesis and interplay with microbiota in human gu
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RESEARCH ARTICLE
Open Access
Spatial and temporal modulation of enterotoxigenic E. coli H10407 pathogenesis and interplay with microbiota in human gut models Charlène Roussel1,2, Kim De Paepe2, Wessam Galia3, Jana De Bodt2, Sandrine Chalancon1, Françoise Leriche4, Nathalie Ballet5, Sylvain Denis1, Monique Alric1, Tom Van de Wiele2*† and Stéphanie Blanquet-Diot1*†
Abstract 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. Keywords: ETEC pathogenesis, Survival, Virulence, Gut microbes, Digestive in vitro systems
* Correspondence: [email protected]; [email protected] † Tom Van de Wiele and Stéphanie Blanquet-Diot contributed equally to this work. 2 CMET, Center for Microbial Ecology and Technology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium 1 Université Clermont Auvergne, UMR UCA-INRA 454 MEDIS, Microbiology Digestive Environment and Health, Clermont-Ferrand, France Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if c
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