title: Gut microbial succession follows acute secretory diarrhea in humans.
abstract: Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea.
  
  
  OBJECTIVE
  Disability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea.
authors.affiliation: Society of Fellows, Harvard University, Cambridge, Massachusetts, USA FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: David
authors.forename: Ana
authors.initials: A
authors.lastname: Weil
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Fahima
authors.initials: F
authors.lastname: Chowdhury
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Begum
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: rclarocque@partners.org Peter.Turnbaugh@ucsf.edu.
authors.forename: Regina C
authors.initials: RC
authors.lastname: LaRocque
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA rclarocque@partners.org Peter.Turnbaugh@ucsf.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Turnbaugh
mesh_terms: D002771:Cholera / Q000382:microbiology*; D003967:Diarrhea / Q000382:microbiology*; D054307:Enterotoxigenic Escherichia coli; D004927:Escherichia coli Infections / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D056186:Metagenomics; D014734:Vibrio cholerae / Q000472:pathogenicity