Abstract
Gut plasmids show heightened sensitivity to gut microenvironmental changes compared to their bacterial hosts. To explore their significance in colorectal cancer (CRC), we analyzed metagenomic data from 863 participants (312 CRC, 387 high-risk, 164 low-risk). Plasmid and bacterial profiles were characterized, along with trace elements and metabolites. Differential analysis, functional gene assessment (ARG, MGE, MRG, VFGB), random forest modeling, and structural equation modeling (SEM) were applied. In terms of overall abundance, plasmids in both the high-risk and CRC groups exhibited a decreasing trend. Gut plasmids significantly influenced the functional genes (ARG, MGE, MRG, VFGB) of their bacterial hosts. Six key bacterial hosts (Enterobacterales, Bucrkholderiales, Hyphomicrobiales, Lactobacillales, Bacteroidales, Campylobacterales) and 12 plasmid markers were identified. The plasmid-based model effectively predicted CRC risk. SEM revealed that trace elements (e.g., Ni), metabolites (e.g., 5-Hydroxytryptophol), and host bacteria (e.g., Campylobacterales, Enterobacterales) predominantly exerted negative effects on most plasmids, whereas Ni exhibited a positive influence on plasmids NZ_CP013564.1, NZ_CP024312.1, and NZ_CP48284.1. We characterized the composition of gut plasmids and their bacterial hosts, explored the impacts of gut plasmids on bacterial functionality, and mapped multi-omics interaction networks linking plasmids, hosts, and metabolic features.
Similar content being viewed by others
Acknowledgements
The authors gratefully thank the patients and volunteers for their contributions to sample collection.
Funding
This work was supported by the Zhejiang Province Traditional Chinese Medicine Science and Technology Project (No. 2025ZL550), Medical and Health Research Project of Zhejiang Province (No.2025KY1531) and Public Welfare Technology Application Research Program of Huzhou (No. 2024GY22).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Consent for publication
Not applicable.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Han, S., Wu, Z., Wu, Y. et al. Decoding the human gut bacterial plasmids in colorectal cancer. Commun Biol (2026). https://doi.org/10.1038/s42003-026-10278-w
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s42003-026-10278-w
