TY - JOUR
T1 - Members of the human gut microbiota involved in recovery from Vibrio cholerae infection
AU - Hsiao, Ansel
AU - Ahmed, A. M.Shamsir
AU - Subramanian, Sathish
AU - Griffin, Nicholas W.
AU - Drewry, Lisa L.
AU - Petri, William A.
AU - Haque, Rashidul
AU - Ahmed, Tahmeed
AU - Gordon, Jeffrey I.
N1 - Funding Information:
Acknowledgements We thank S. Wagoner, J. Hoisington-López, M. Meier, J. Cheng, D. O’Donnell, and M. Karlsson for technical support, J. Zhu for providing strains of V.choleraeandVibrio harveyi, and W.-L. Ngfor providing DluxP V. cholerae. Thiswork was supported in part by a grant from the Bill & Melinda Gates Foundation. The singleton birth cohort of Bangladeshi children was supported by a grant from the National Institutes of Health (AI 43596). The post-doctoral fellowship stipend of A.H. was funded in part by NIH training grants (T32DK077653, T32AI007172) and by the Crohn’s and Colitis Foundation of America. The International Centre for Diarrhoeal Disease Research, Bangladesh, acknowledges the following donors, which provided unrestricted support: the Australian Agency for International Development, the Government of Bangladesh, the Canadian International Development Agency, the Swedish International Development Cooperation Agency, and the Department for International Development, UK.
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014/11/20
Y1 - 2014/11/20
N2 - Given the global burden of diarrhoeal diseases, 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. 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. 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. One of the species, Ruminococcus obeum, exhibits consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obeum 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. cholerae mutants 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.
AB - Given the global burden of diarrhoeal diseases, 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. 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. 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. One of the species, Ruminococcus obeum, exhibits consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obeum 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. cholerae mutants 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.
UR - http://www.scopus.com/inward/record.url?scp=84911468185&partnerID=8YFLogxK
U2 - 10.1038/nature13738
DO - 10.1038/nature13738
M3 - Article
C2 - 25231861
AN - SCOPUS:84911468185
SN - 0028-0836
VL - 515
SP - 423
EP - 426
JO - Nature
JF - Nature
IS - 7527
ER -