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Abstract The human gut microbiome is composed of a highly diverse consortia of species that are continually evolving within and across hosts1,2. The ability to identify adaptations common to many human gut microbiomes would show not only shared selection pressures across hosts but also key drivers of functional differentiation of the microbiome that may affect community structure and host traits. However, the extent to which adaptations have spread across human gut microbiomes is relatively unknown. Here we develop a new selection scan statistic named the integrated linkage disequilibrium score (iLDS) that can detect sweeps of adaptive alleles spreading across host microbiomes by migration and horizontal gene transfer. Specifically, iLDS leverages signals of hitchhiking of deleterious variants with a beneficial variant. Application of the statistic to around 30 of the most prevalent commensal gut species from 24 human populations around the world showed more than 300 selective sweeps across species. We find an enrichment for selective sweeps at loci involved in carbohydrate metabolism, indicative of adaptation to host diet, and we find that the targets of selection differ significantly between industrialized populations and non-industrialized populations. One of these sweeps is at a locus known to be involved in the metabolism of maltodextrin—a synthetic starch that has recently become a widespread component of industrialized diets. In summary, our results indicate that recombination between strains fuels pervasive adaptive evolution among human gut commensal bacteria, and strongly implicate host diet and lifestyle as critical selection pressures.
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This content will become publicly available on February 1, 2026
Inference of the Demographic Histories and Selective Effects of Human Gut Commensal Microbiota Over the Course of Human History
Abstract Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their demographic histories and distributions of fitness effects (DFEs) of mutations. Here, we infer the demographic histories and DFEs for amino acid-changing mutations of 39 of the most prevalent and abundant commensal gut microbial species found in Westernized individuals over timescales exceeding human generations. Some species display contractions in population size and others expansions, with several of these events coinciding with several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with differences between accessory and core gene DFEs largely driven by genetic drift. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Together, these findings suggest that gut microbes have distinct demographic and selective histories.
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- Award ID(s):
- 2240098
- PAR ID:
- 10654868
- Editor(s):
- Hepp, Crystal
- Publisher / Repository:
- Molecular Biology and Evolution
- Date Published:
- Journal Name:
- Molecular Biology and Evolution
- Volume:
- 42
- Issue:
- 2
- ISSN:
- 0737-4038
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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