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bioRxiv · 10.64898/2026.10.01.755998

Community-wide adaptive evolution of gut bacteria during dietary transitions

Hernandez, S. G.·Uppal, S.·Jin, D.-M.·Landers, A. A.·Ennis, N.·Sprockett, D. D.·Moeller, A. H.
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Abstract

Diet exerts selection on bacterial species within the mammalian gut microbiota1,2,3,4,5, but the extent, modes, genomic bases, and repeatability of gut bacterial adaptive evolution in response to dietary variation within hosts are poorly understood. Here, we show that within-host dietary transitions drive ubiquitous and highly reproducible adaptive evolution of gut bacterial populations. We deeply profiled allele-frequency dynamics in gut microbiota of an experimental cohort of litter-matched wild-derived isogenic mice either transitioned from low-fat/high-carbohydrate diets to high-fat/low-carbohydrate diets or maintained on their ancestral low-fat/high-carbohydrate diet. Dietary transitions induced significantly parallel allele-frequency changes across replicates in 61/62 core gut bacterial species within five months, whereas 0/62 species displayed significant across-replicate parallelism in the control group, indicating deterministic adaptive evolutionary responses across the gut microbiota. Adaptation proceeded through multiple modes, including strain sorting and gene-wise responses. The latter were enriched in a subset of gene families and functions across bacterial species, including invertases. Culturing revealed an invertible DNA switch in Phocaeicola sartorii that, in all replicates transitioned to high-fat/low-carbohydrate diets, localized a promoter sequence upstream of cell-surface glycan foraging genes. These findings elucidate widespread gut bacterial adaptive evolution mediated by within-host dietary variation.

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Hernandez, S. G., Uppal, S., Jin, D.-M., Landers, A. A., Ennis, N., Sprockett, D. D., Moeller, A. H.. 2026-10-04. Community-wide adaptive evolution of gut bacteria during dietary transitions. https://doi.org/10.64898/2026.10.01.755998

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