Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production
Open accessAbstract
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.
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Some intervention and cross-sectional studies found only modest microbiota differences between omnivores and vegetarians, with the largest effects at genus and species level and little effect on broader measures such as diversity and richness.
“some intervention and cross-sectional studies have observed only modest microbiota differences between omnivores and vegetarians and suggest that the effects of dietary pattern on the microbiota are greatest at the genus and species level and relatively minimal on broader compositional features, such as diversity and richness (65–67)”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [67]
Long-term dietary habits are a dominant determinant of an individual's gut microbiota composition.
“long-term dietary habits are a dominant force in determining the composition of an individual’s gut microbiota”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [28]
Negligible differences were recently found between the gut microbiota of a small US cohort of omnivores and vegans.
“Negligible differences were recently found between the gut microbiota of a small-size cohort of omnivore and vegan individuals in the USA.7”
From High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome (2016) · cites this paper as [7]
Wu et al reported negligible differences in faecal microbiota composition and plasma SCFA profiles in 15 vegan and 16 omnivore subjects, and found no evidence for diet-driven separations in either measure.
“Wu et al 7 recently reported negligible differences in the faecal microbiota composition and plasma SCFA profiles in 15 vegan and 16 omnivore subjects, and found no evidence for dietdriven separations in either measure.”
From High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome (2016) · cites this paper as [7]
Prevotella levels were not significantly different between omnivores and vegans.
“Levels of Prevotella were not significantly different between omnivores and vegans.7”
From High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome (2016) · cites this paper as [7]
Higher median intake of fibre and starch was recorded in both omnivore and vegan subjects compared with the US cohort.
“Interestingly, we recorded higher median intake of fibre and starch in both omnivore and vegan subjects compared with the US cohort.7”
From High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome (2016) · cites this paper as [7]
The diet-microbe interaction is highly personalized and dependent on the baseline microbiota present.
“Although some generalizations about the impact of diet on microbiota composition can be made, recent work also suggests that the diet-microbe interaction is highly personalized and dependent on the baseline microbiota present (110)”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [110]
Considerable variations were observed in the bacterial metabolome, suggesting that diet as a substrate may play a larger role in determining microbial metabolite production than in microbial composition itself.
“However, considerable variations were observed in the bacterial metabolome, suggesting that diet as a substrate may play a larger role in determining microbial metabolite production than in the microbial composition itself.”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [110]
Data regarding the impact of plant-based compared with animal-based diets on the microbiota are still not conclusive.
“Nevertheless, the data regarding the impact of plant-based compared with animal-based diets on the microbiota are still not conclusive, as evidenced by a human study indicating that the microbial composition was only modestly different between vegans and omnivores (110).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [110]
Long-term dietary habits play a role in shaping the composition and metabolic activity of the gut microbiota.
“Previous studies have suggested that long-term dietary habits play a role in shaping the composition and metabolic activity of the gut microbiota.”
From Adaptation to tolerate high doses of arabinoxylan is associated with fecal levels of <i>Bifidobacterium longum</i> (2024) · cites this paper as [66]
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- Authors
- Wu, G. D., Compher, C., Chen, E. Z., Smith, S. A., Shah, R. D., Bittinger, K., Chehoud, C., Albenberg, L. G., Nessel, L., Gilroy, E., Star, J., Weljie, A. M., Flint, H. J., Metz, D. C., Bennett, M. J., Li, H., Bushman, F. D., & Lewis, J. D.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- University of Aberdeen (GB)
- Corresponding author
- Wu, Gary D
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2014-11-26
- Volume
- 65
- Issue
- 1
- Pages
- 63-72
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC4583329
- OpenAlex
- W2061853512
- Cited by
- 512
- References
- 54
- Citations by year
- 2026: 15 · 2025: 34 · 2024: 38 · 2023: 35 · 2022: 63 · 2021: 58 · 2020: 62 · 2019: 50 · 2018: 59 · 2017: 42 · 2016: 32 · 2015: 21 · 2014: 1 · 2013: 1
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- Scottish Government
- National Institutes of Health (DK050306)
- National Institute of General Medical Sciences (R01GM103591)
- National Institute of Allergy and Infectious Diseases (T32AI007632)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089472, UH2/3 DK083981, UH3DK083981, UH2DK083981, K23DK095913, P30DK050306)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- vegan diet, omnivorous diet, gut microbiota, urinary metabolome, short-chain fatty acids, equol, soy isoflavones
- MeSH terms
- Diet, Vegan, Gastrointestinal Microbiome, Cross-Sectional Studies, Diet, Feces, Humans, United States, Urban Health, Metabolomics, Metabolome
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