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. 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.

Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity

“…A metabolomics study in humans identified Hyp as a top plasma biomarker for distinguishing omnivores from vegans due to its higher abundance in omnivores. 43 This finding supports the proposal that diet is a significant source of Hyp and is potentially in agreement with the higher Hyp content of meat as compared to plant material. This result may also suggest that dietary changes affect the degree to which gut microbes and/or the host metabolize Hyp.…”

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

“…This metabolite is produced by the gut microflora (11), and higher serum concentrations are associated with various health outcomes such as periodontal disease and lean body mass in animals or humans (12)(13)(14)(15)(16). 4-Ethylphenylsulfate is correlated with the consumption of soy products (17,18) and is elevated in the plasma of vegans compared with omnivores; a vegan diet increases concentrations of several products produced by the gut microbiota (19). Salt has known antibacterial properties (20) and has been used for medicinal purposes for centuries (21,22).…”

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

“…It was not possible to explain the small difference in microbiota composition associated with such substantial differences in diet, but it was suggested that if differences in microbiota observed in globally distinct human populations are attributable to differences in diet then possibly these differences take several generations to develop, or 19 possibly the young must be exposed to the different diet at an early age. Another possibility suggested was an environmental factor other than diet [129].…”