Members of the human gut microbiota involved in recovery from Vibrio cholerae infection

作者：Hsiao Ansel; Ahmed A M Shamsir; Subramanian Sathish; Griffin Nicholas W; Drewry Lisa L; Petri William A Jr; Haque Rashidul; Ahmed Tahmeed; Gordon Jeffrey I^*

来源：Nature, 2014, 515(7527): 423-+.

DOI：10.1038/nature13738

Given the global burden of diarrhoeal diseases(1), it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhoea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. Here we conduct a detailed time-series metagenomic study of faecal microbiota collected during the acute diarrhoeal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease(2). We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children(3). To define the underlying mechanisms, we introduce into gnotobiotic mice an artificial community composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children(3). One of the species, Ruminococcus obe urn, exhibits consistent increases in its relative abundance upon V. choleraeinfection of the mice. Follow-up analyses, including mono-and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obewn luxS (autoinducer-2 (AI-2) synthase) expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing-mediated repression of several V. cholerae colonization factors. Co-colonization with V. choleraemutants discloses that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

• 出版日期2014-11-20