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Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production
  1. Gary D Wu1,
  2. Charlene Compher2,
  3. Eric Z Chen3,
  4. Sarah A Smith1,
  5. Rachana D Shah4,
  6. Kyle Bittinger5,
  7. Christel Chehoud5,
  8. Lindsey G Albenberg6,
  9. Lisa Nessel3,
  10. Erin Gilroy3,
  11. Julie Star1,
  12. Aalim M Weljie7,
  13. Harry J Flint8,
  14. David C Metz1,
  15. Michael J Bennett9,
  16. Hongzhe Li3,
  17. Frederic D Bushman5,
  18. James D Lewis1,3
  1. 1Division of Gastroenterology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2School of Nursing, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. 3Departments of Biostatistics & Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. 4Divisions of Endocrinolgy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  5. 5Department of Microbiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
  6. 6Department of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  7. 7Department of Pharmacology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
  8. 8Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
  9. 9Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  1. Correspondence to Gary D Wu, 915 BRB II/III, 421 Curie Blvd, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; gdwu{at}mail.med.upenn.edu James D Lewis, 720 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021; lewisjd{at}mail.med.upenn.eduFrederic D Bushman, 426 Johnson Pavilion, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104-6076; bushman{at}mail.med.upenn.edu

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.

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.

Keywords
  • gut
  • microbiota
  • metabolome
  • bacteria
  • diet

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