Abstract
Emerging evidence suggests that tissue-resident microbiota (TRM) is associated with tumor biology; however, their distribution and compositional characteristics across different colorectal tissue types remain incompletely defined. Here, we conducted a comprehensive cross-sectional analysis of TRM distribution and abundance across 1134 clinical specimens, including normal mucosa, precancerous polyps, and colorectal cancer (CRC) tissues. Our results reveal distinct microbial profiles among these diagnostic groups, with consistent differences in community composition between normal, polyps, and CRC samples. Integrative analyses further identified microbial signatures capable of distinguishing tissue categories and reflected differences in the local tumor microenvironment. In contrast, intratumoral microbiota composition showed subtle variation across established tumor stages and was not associated with clinical outcomes. These findings define diagnostic group-associated patterns of TRM in colorectal tissues and establish a foundation for future mechanistic investigations into the biological roles of TRM in colorectal cancer.
Data availability
The data generated in this study is available at https://github.com/Lingning927/microbioInCRC. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2021) in the National Genomics Data Center (Nucleic Acids Res 2022), China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: CRA025367) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa. The fecal sample cohort of CRC patients was sourced from the NCBI database, with accession code PRJEB10878, PRJEB27928 [DOI: 10.1038/s41591-019-0406-6], PRJEB7774, PRJEB12449, PRJDB4176, PRJEB6070 and PRJNA447983. Source data are provided with this paper.
Code availability
All R scripts used for the analysis and plotting in this study are available in the GitHub repository (https://github.com/Lingning927/microbioInCRC) and are permanently archived on Zenodo (https://doi.org/10.5281/zenodo.18015706).
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Acknowledgements
This research was partially supported by the National Natural Science Foundation of China (nos. 82273265, 32271213 and 32471189), Department of Science and Technology of Zhejiang Province (2023C03065 and 2025C02128), Zhejiang Provincial Major Medical and Health Science and Technology Program (WKJ-ZJ-2504), Zhejiang Provincial Administration of Traditional Chinese Medicine co-constructs scientific and technological projects (GZY-ZJ-KJ-23029), and High-level Talent Special Support Program of Zhejiang Province.
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Z.S. and Y.W. designed the study. Z.S., Y.W., H.J., and H.C. initiated and directed the project. W.L., M.C., B.B., and H.X. collected the samples. H.C. managed the 16S rRNA sequencing library construction. H.X. and B.S. completed the experiment, performed the bioinformatic analyses, and prepared the figures. W.Z., G.Y,. and L.Z. provided samples of the Changhai cohort. All authors contributed to the writing and revision of the manuscript.
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Xiang, H., Shen, B., Lao, W. et al. The landscape of tissue-resident microbiota across normal, polyp, and colorectal cancer tissues. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69705-5
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DOI: https://doi.org/10.1038/s41467-026-69705-5
