BACKGROUND Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels. RESULTS Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice. CONCLUSIONS Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.

中文翻译：

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共生衍生的代谢物控制宿主肠道中霍乱弧菌的发病机制。

背景最近的证据表明，共生微生物作为入侵病原体的屏障，肠道感染是共生微生物、病原体和宿主肠道组织之间多层相互作用的结果。然而，目前尚不清楚肠道微生物群的扰动如何损害宿主的感染抵抗力，特别是通过物种和代谢水平的变化。结果在这里，我们说明了普通拟杆菌（小鼠肠道拟杆菌门的优势种）如何抑制霍乱弧菌（一种重要的人类病原体）的感染。克林霉素 (CL) 是一种选择性杀死厌氧菌的抗生素，因此经过 CL 处理的小鼠肠道中的拟杆菌被完全根除。当感染霍乱弧菌时，拟杆菌被清除的成年小鼠出现严重的霍乱样症状。与普通双歧杆菌单一相关的无菌小鼠对霍乱弧菌感染产生了抵抗力。CL处理后，霍乱弧菌生长抑制代谢物（包括短链脂肪酸）的水平急剧下降，而促进霍乱弧菌增殖的化合物的水平则升高。此外，霍乱弧菌的肠道定植过程在 CL 处理的成年小鼠中得到了很好的模拟。结论总的来说，我们深入了解了共生微生物和致病入侵者如何在宿主肠道内相互作用。我们确定普通双歧杆菌是一种可以抑制肠道感染的本土微生物物种。我们的结果还表明，共生源代谢物是宿主抵抗霍乱弧菌感染的关键决定因素，并且对成年小鼠进行 CL 预处理可产生简单但有用的霍乱感染模型。