Diet leaves a genetic signature in a keystone member of the gut microbiota. Dapa et al.

Published: 17 January 2022| Version 1 | DOI: 10.17632/p57zpdc359.1


Dietary switch from a low-fat and high-fiber diet to a Western-style high-fat and high-sugar diet is a common cause of microbiota imbalances underlying a variety of pathological conditions (i.e. dysbiosis). Although the effects of such dietary changes on microbiota composition and functions are well documented, their putative impact in gut bacterial evolution remains unexplored. We reasoned that the microbiota-dependent functional consequences observed in diet-induced dysbiosis could be caused not only by changes in microbiota composition and in gene/metabolic regulation, but also by evolutionary changes, via the emergence of de novo mutations, which can lead to intra-species changes. To address this hypothesis, we determined the effects of diet on mutational changes in genes at the single species level by monitoring evolutionary adaptation to the gut of mice undergoing different dietary regimens. We focused on Bacteroides thetaiotaomicron (hereafter referred as B. theta) due to its predominance in the mammalian gut. B. theta is a strict anaerobe, and is among the fiber degrading Bacteroides that in the absence of dietary plant polysaccharides can consume host glycans. This bacterium shows phenotypic plasticity by gene and metabolic regulatory mechanisms, which enable it to prioritize usage of carbon sources, and to consume host glycans only in the absence of dietary complex polysaccharides. By following the evolutionary dynamics of B. theta over a 3-month timescale, we observe genetic signatures resulting from diet-specific evolution, fluctuating rapidly as the diet consumed by the mice alternates from high in fat and sugar and low in fiber (Western-style Diet (WD)) to standard high-fiber chow diet (Standard Diet (SD)). Periodic changes in diet led to fluctuations in the frequency of such mutations and were associated with metabolic shifts, resulting in the maintenance of higher intra-species genetic diversity compared to constant dietary regimens. We show that adaptation under WD specifically favors the emergence of mutations advantageous in consumption of mucin O-glycans. This supports the hypothesis that intra-species evolution can influence the microbiota-dependent phenotypes observed upon dietary changes. Finally, through an integrative multi-omic analysis, combining metabolomic and microbiota profiling with the B. theta mutational profile, we show that intra-species mutational diversity is a powerful biomarker of dietary differences between individuals.


Steps to reproduce

Read first the file named "1.0_Read_First". File "1.0_Read_First" describes which of the files corresponds to which figure.


Instituto Gulbenkian de Ciencia


Microbiota, Database