Abstract
While environmental gradients are known to result in heterogeneous distributions of bacterial species along the gastrointestinal tract, the spatial distribution of genetic diversity within these species remains poorly understood. Because bacterial genetic variants influence host traits like inflammation and metabolism, understanding their distribution is critical. Here, we analyze ~30 common gut commensals in germ-free mice colonized with the same healthy human stool. Unexpectedly, we find that while species composition varied significantly across gut regions, genetic diversity within species remained remarkably uniform. This uniformity is driven by similar strain frequencies along the gut lumen, indicating that genetically divergent strains can coexist without spatial segregation. Furthermore, ~60 evolutionary adaptations arising within the mice tend to sweep globally throughout the gut, showing little region-specificity. We observe similar dynamics in conventional mice and humans, suggesting that uniform bacterial genetic diversity is a conserved, robust feature of mammalian gut ecosystems.
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Data availability
The raw metagenomics sequencing reads data generated in this study have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject accession number PRJNA1230553. The processed count tables, associated metadata, and other data tables used to produce figures are available in Supplementary Information.
Code availability
All necessary metadata, as well as the source code for the sequencing pipeline, downstream analyses, and figure generation, are available on GitHub (https://github.com/garudlab/Wasney-Briscoe/).
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Acknowledgements
The authors thank Kristin Harper, PhD, of Harper Health & Science Communications, LLC, for providing editorial support in accordance with Good Publication Practice guidelines, and Alison Feder, PhD, for her helpful edits. The authors also thank the Garud and the Tropini labs for their valuable inputs. In particular, the authors thank Peter Laurin for his statistical advice and feedback on the manuscript. Finally, the authors thank Dr. Sidhartha Sinha and members of the Sinha Lab at Stanford University for helpful discussions. This work was funded by NIGMS NIH award R35GM151023 (to N.R.G.), NSF CAREER award (no. 2240098, to N.R.G), a Paul Allen Distinguished Investigator Award (to C.T. and N.R.G.), a Canadian Institutes of Health Research Team Grant: Canadian Microbiome Initiative 2 (to C.T.), Crohn’s and Colitis Canada, Canadian Institute for Advanced Research (to C.T.), the Michael Smith Foundation for Health Research Scholar Award (18239, to C.T.), Canada Foundation for Innovation/Infrastructure Operating Fund (38277, to C.T.), Canada Tier 2 Research Chair, Quantitative Microbiota Biology for Health Applications (CRC-2022-00036, to C.T.), Canadian Institute for Advanced Research/Humans and the Microbiome (FL-001253 Appt 3362, to C.T.), and the 4-Year Fellowship (to H.G.).
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N.R.G. conceived of the study. M.W., L.B., and N.R.G planned all analyses. M.W. and L.B. completed analyses and wrote all code associated with this study, with code and conceptual contributions from R.W. for the strain frequency estimation analyses. H.G. completed the mouse experiments and DNA extraction. M.W., L.B., C.T, and N.R.G. wrote the manuscript. All authors approved the final version of the manuscript.
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Wasney, M., Briscoe, L., Wolff, R. et al. Uniform bacterial genetic diversity along the gut. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70705-8
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DOI: https://doi.org/10.1038/s41467-026-70705-8
