title: Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production.
abstract: OBJECTIVE
  The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a 'Westernised' lifestyle. Studies suggest that diet affects the gut microbiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gut microbiota is controversial. Murine models and studies comparing the gut microbiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gut microbiota and the host metabolome of individuals consuming an agrarian diet in Western society.
  
  
  RESULTS
  Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gut microbiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gut microbiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gut microbiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products.
  
  
  CONCLUSIONS
  Evidently, residence in globally distinct societies helps determine the composition of the gut microbiota that, in turn, influences the production of diet-dependent gut microbial metabolites.
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
authors.affiliation: School of Nursing, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Charlene
authors.initials: C
authors.lastname: Compher
authors.affiliation: Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Eric Z
authors.initials: EZ
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Divisions of Endocrinolgy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Rachana D
authors.initials: RD
authors.lastname: Shah
authors.affiliation: Department of Microbiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bittinger
authors.affiliation: Department of Microbiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Christel
authors.initials: C
authors.lastname: Chehoud
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Lindsey G
authors.initials: LG
authors.lastname: Albenberg
authors.affiliation: Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Gilroy
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Star
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Aalim M
authors.initials: AM
authors.lastname: Weljie
authors.affiliation: Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Flint
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Metz
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bennett
authors.affiliation: Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Microbiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Frederic D
authors.identifier: http://orcid.org/0000-0003-4740-4056
authors.initials: FD
authors.lastname: Bushman
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D003430:Cross-Sectional Studies; D004032:Diet; D000067269:Diet, Vegan; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D014481:United States; D014504:Urban Health
keywords: bacteria; diet; gut; metabolome; microbiota