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Original Article | Open Access

Comprehensive microbiome profiling reveals mucosal microbiome heterogeneity in patients with left- and right-sided colorectal neoplasia

Sunny H. Wong1,2Thomas N.Y. Kwong3Ru Zhang3,4Thomas Y.T. Lam5Andrew M.Y. Ho3Wing Wah Leung6Xing Kang1,3Harry C.H. Lau3Eagle S.H. Chu3Marc T.L. Wong3Louis H.S. Lau3Rashid N.S. Lui3Raymond S.Y. Tang3James Y.W. Lau6Simon S.M. Ng6Jun Yu3,7Joseph J.Y. Sung1,2 ( )
Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, National Healthcare Group, Singapore 308433, Singapore
Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Shenzhen People’s Hospital, Shenzhen 518020, China
The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
CUHK-Shenzhen Research Institute, Shenzhen 518057, China
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Abstract

Objective

Left- and right-sided colorectal cancer (CRC) exhibit distinct molecular and clinicopathologic features. However, little is known about the spatial heterogeneity of microbial signatures. In this study the profiles and ecologic patterns of disease-associated intestinal microbiome were investigated in patients with an adenoma(s) or CRC at different anatomic locations.

Methods

A total of 690 stool, colonic aspirate, and mucosal biopsy samples were prospectively collected from 32 healthy, 30 adenoma, and 31 CRC patients.

Results

CRC was associated with alterations in fecal and mucosal microbiomes. Furthermore, the overall composition of the mucosal microbiome, stratified by metacommunities, differed between the patients with left- and right-sided neoplastic lesions. Patients with right-sided CRC had an elevated inter-phylum ecologic network, while patients with left-sided CRC had an enriched abundance of Fusobacterium. Interestingly, rectal neoplasia harbored a tumor microbiome that was distinctly different from the tumor microbiome at other anatomic sites.

Conclusion

The mucosal microbiome of right-sided CRC was distinctly different from the mucosal microbiome of left-sided CRC patients, suggesting distinct microbial ecology and heterogeneous host-microbial ecologic relationships that may contribute to differences in the tumor microenvironment between left- and right-sided CRC.

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Cancer Biology & Medicine
Pages 755-768

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Cite this article:
Wong SH, Kwong TN, Zhang R, et al. Comprehensive microbiome profiling reveals mucosal microbiome heterogeneity in patients with left- and right-sided colorectal neoplasia. Cancer Biology & Medicine, 2026, 23(5): 755-768. https://doi.org/10.20892/j.issn.2095-3941.2025.0846

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Received: 08 January 2026
Accepted: 25 March 2026
Published: 26 May 2026
©2026 The Authors.

Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)