Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production

Gary D Wu, Charlene Compher, Eric Z Chen, Sarah A Smith, Rachana D Shah, Kyle Bittinger, Christel Chehoud, Lindsey G Albenberg, Lisa Nessel, Erin Gilroy, Julie Star, Aalim M Weljie, Harry J Flint, David C Metz, Michael J Bennett, Hongzhe Li, Frederic D Bushman, James D Lewis

Research output: Contribution to journalArticlepeer-review

379 Citations (Scopus)


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.

DESIGN AND 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.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
Issue number1
Early online date26 Nov 2014
Publication statusPublished - Jan 2016

Bibliographical note

Acknowledgements: This work was supported by Project NIH UH2/3 DK083981 and administrative supplement 04S1 (GDW, FDB and JDL), Scottish Government Food, Land and People programme (HJF), The Molecular Biology Core of the Penn Center for the Molecular Studies in Digestive and Liver Diseases (P30 DK050306), The Joint Penn-CHOP Center for Digestive, Liver and Pancreatic Medicine and Penn Vegan Society.

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