title: Members of the human gut microbiota involved in recovery from Vibrio cholerae infection.
abstract: 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.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
authors.forename: Ansel
authors.initials: A
authors.lastname: Hsiao
authors.affiliation: 1] School of Population Health, The University of Queensland, Brisbane, Queensland 4006, Australia [2] Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh.
authors.forename: A M Shamsir
authors.initials: AM
authors.lastname: Ahmed
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
authors.forename: Sathish
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Griffin
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Drewry
authors.affiliation: 1] Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA [2] Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA [3] Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
authors.affiliation: Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Dhaka 1212, Bangladesh.
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001459:Bangladesh; D002648:Child; D002771:Cholera / Q000382:microbiology*; D015331:Cohort Studies; D003967:Diarrhea / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005856:Germ-Free Life; D006262:Health; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000235:genetics; D051379:Mice; D064307:Microbiota / Q000235:genetics / Q000502:physiology*; D053038:Quorum Sensing / Q000502:physiology; D045857:Ruminococcus / Q000302:isolation & purification / Q000502:physiology*; D014734:Vibrio cholerae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D037521:Virulence Factors