Université Clermont Auvergne, UMR UCA-INRA 454 MEDIS, Microbiology Digestive Environment and Health, Clermont-Ferrand, France.
CMET, Center for Microbial Ecology and Technology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
BMC Biol. 2020 Oct 14;18(1):141. doi: 10.1186/s12915-020-00860-x.
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).
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 log mL 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.
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.
产肠毒素性大肠杆菌（ETEC）是发展中国家腹泻病负担的主要原因。本研究利用人类消化环境的体外互补模型，即 TNO 胃肠道模型（TIM-1）和人类肠道微生物生态系统黏膜模拟器（M-SHIME），首次详细报告了 ETEC H10407 存活、毒力及其与肠道微生物群相互作用的时空调节。这些系统整合了人类上消化道的主要理化参数（TIM-1），并模拟了回肠与升结肠微生物群落以及来自六位粪便供体的腔和黏膜微环境（M-SHIME）。
胃消化过程中观察到 ETEC 活力丧失，而在空肠和回肠消化结束时发现了生长恢复。显著的 ETEC 黏膜附着有助于在感染后 5 天内将肠腔内浓度保持在 6 log mL 以上。监测了 7 种 ETEC 毒力基因。大多数基因在胃中开启，在 TIM-1 回肠流出物中关闭，并在 M-SHIME 升结肠的感染后期关闭。与回肠和升结肠不同，在胃中未测量到不耐热肠毒素的产生。使用 16S rRNA 基因扩增子测序，ETEC 感染调节了回肠黏液和升结肠腔的微生物群落结构。
本研究更好地理解了 ETEC 与胃肠道线索之间的相互作用，并可能有助于完善 ETEC 发病机制的知识，并为腹泻病提供新的预防策略。
