Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production - PubMed (original) (raw)

Comparative Study

doi: 10.1136/gutjnl-2014-308209. Epub 2014 Nov 26.

Charlene Compher 2, Eric Z Chen 3, Sarah A Smith 1, Rachana D Shah 4, Kyle Bittinger 5, Christel Chehoud 5, Lindsey G Albenberg 6, Lisa Nessel 3, Erin Gilroy 3, Julie Star 1, Aalim M Weljie 7, Harry J Flint 8, David C Metz 1, Michael J Bennett 9, Hongzhe Li 3, Frederic D Bushman 5, James D Lewis 10

Affiliations

Comparative Study

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

Gary D Wu et al. Gut. 2016 Jan.

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: bacteria; diet; gut; metabolome; microbiota.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PubMed Disclaimer

Conflict of interest statement

Competing interests: None.

Figures

Figure 1

Figure 1

Dietary consumption comparison between omnivores and vegans residing in an urban US environment. (A) Principle component analysis of dietary micronutrient consumption in omnivores versus vegans. (B) Heat map dietary micronutrients in omnivores (purple) versus vegans (green) colour coded by seven major nutrient categories. Red=higher abundance, blue=lower abundance, p values as indicated by the number of asterisks. PC, principle component.

Figure 2

Figure 2

The composition of the gut microbiota in omnivore versus vegans show very modest differences. Multidimensional scaling (MDS) analysis of gut microbiota composition in omnivore versus vegans determined by 16S rRNA gene sequencing by (A) unweighted UniFrac distance (PERMANOVA p=0.007), (B) weighted UniFrac distance (PERMANOVA p=0.15). (C) Comparison of Simpson diversity index in omnivores versus vegans (p=0.53).

Figure 3

Figure 3

Comparison of plasma metabolites in omnivores versus vegans. (A) Hierarchical clustering correlating levels of plasma metabolites between omnivores versus vegans visualised as a heatmap. Red=higher abundance, blue=lower abundance. (B) Random forest classification of 30 plasma metabolites, categorised into seven areas (colour coded), capable of distinguishing an omnivore from a vegan with a predictive accuracy of 94%. (C) Targeted quantification of urinary metabolites in omnivores and vegans visualised in a principal components analysis biplot that displays the correlation of each sample with the metabolite descriptors. Metabolite descriptors are represented by arrows pointing in the direction of maximum correlation with the samples.

Figure 4

Figure 4

Plasma levels of plasma metabolites in omnivores and vegans derived from gut microbiota metabolism of plant polyphenolic compounds. *p<0.1, **p<0.05.

Figure 5

Figure 5

Association between the consumption of dietary substrates used by the gut microbiota to produce equol showing the standardised intake of diadzein and geneistein in omnivores and vegans with and without detectable plasma levels of equol.

Figure 6

Figure 6

Model describing the relationship between substrate abundance and gut microbiota product formation and its dependence on gut microbiota composition using the consumption of fermentable carbohydrates and the production of short chain fatty acids (SCFAs) as an example. Herbivorous mammals and humans residing in agrarian societies, with a predominance of gut bacteria capable of producing SCFAs through fermentation, have a ‘permissive’ community structure of their gut microbiota and exhibit substrate-dependent production of product that is linear. By contrast, residence of humans in Westernised societies have a ‘restrictive community structure’ where additional substrate delivery leads to a minimal increase in product formation due to saturation. However, both community structures are substrate-dependent whereby a decrease in substrate consumption (ie, omnivores on a low carbohydrate/fibre diet) will lead to a decrease in product formation (SCFAs).

Comment in

References

    1. Ley RE, Hamady M, Lozupone C, et al. Evolution of mammals and their gut microbes. Science. 2008;320:1647–51. - PMC - PubMed
    1. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107:14691–6. - PMC - PubMed
    1. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–7. - PMC - PubMed
    1. Muegge BD, Kuczynski J, Knights D, et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011;332:970–4. - PMC - PubMed
    1. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716–24. e1–2. - PMC - PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources