Tissue-resident microbiota impacts colorectal cancer progression and prognosis

Zhun Shi; Huahui Ren; Cong Lin; Fuqiang Li; Meizhen Wu; Fangming Yang; Tian Luo; Luís Nunes; Anders Isaksson; Klara Hammarström; Ting Zhu; Shida Zhu; Yiyi Zhong; Ingrid Ljuslinder; Mathias Uhlén; Richard Palmqvist; Bengt Glimelius; Kui Wu; Tobias Sjöblom; Huanzi Zhong

doi:10.1038/s41467-025-67047-2

Tissue-resident microbiota impacts colorectal cancer progression and prognosis

Nat Commun. 2025 Dec 7;17(1):346. doi: 10.1038/s41467-025-67047-2.

Authors

Zhun Shi^#¹, Huahui Ren^#¹, Cong Lin^#^{2

3}, Fuqiang Li^#^{4

5}, Meizhen Wu¹, Fangming Yang¹, Tian Luo¹, Luís Nunes^{6

7}, Anders Isaksson⁷, Klara Hammarström⁷, Ting Zhu⁸, Shida Zhu¹, Yiyi Zhong^{1

9}, Ingrid Ljuslinder¹⁰, Mathias Uhlén^{11

12}, Richard Palmqvist¹³, Bengt Glimelius⁷, Kui Wu¹⁴, Tobias Sjöblom¹⁵, Huanzi Zhong^{16

17}

Affiliations

¹ BGI Genomics, Shenzhen, China.
² HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, BGI Research, Hangzhou, China. lincong@genomics.cn.
³ Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen, China. lincong@genomics.cn.
⁴ HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, BGI Research, Hangzhou, China.
⁵ Guangdong Provincial Key Laboratory of Human Disease Genomics, BGI Research, Shenzhen, China.
⁶ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
⁷ Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁸ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
⁹ BGI Precision Nutrition, Shenzhen, China.
¹⁰ Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
¹¹ Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden.
¹² Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹³ Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
¹⁴ BGI Genomics, Shenzhen, China. wukui@genomcis.cn.
¹⁵ Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. tobias.sjoblom@igp.uu.se.
¹⁶ BGI Genomics, Shenzhen, China. zhonghuanzi@genomics.cn.
¹⁷ BGI Precision Nutrition, Shenzhen, China. zhonghuanzi@genomics.cn.

^# Contributed equally.

Abstract

To deepen the understanding of tissue-resident microbiota in colorectal cancer (CRC), we analyzed whole-genome and transcriptome data from 937 patients. We identified 249 genera and 361 species commonly present in both tumors and adjacent normal tissues (NATs). Distinct microbial signatures were associated with anatomical location, tumor stages, hypermutation status, mutations in CRC driver and DNA damage repair genes, as well as consensus molecular subtypes (CMSs). Notably, the presence of the pks island and elevated abundance of Enterobacteriaceae were linked to poor prognosis specifically in CMS2 tumors. Finally, microbial risk scores derived from taxa present in tumor or NATs predicted patient prognosis independently of established clinico-molecular factors. Prognostic taxa were strongly associated with tumor transcriptomic pathways related to hypoxia, immune response, and metabolic status. These findings revealed the heterogeneity of tissue-resident microbiota and their critical role in CRC progression, highlighting potential avenues for targeted intervention.

MeSH terms

Aged
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / microbiology
Colorectal Neoplasms* / mortality
Colorectal Neoplasms* / pathology
Disease Progression
Female
Gastrointestinal Microbiome* / genetics
Humans
Male
Microbiota* / genetics
Middle Aged
Mutation
Prognosis
Transcriptome