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

Sep 22, 2026

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Left- and right-sided colorectal cancer (CRC) show distinct molecular and clinicopathologic features, yet spatial heterogeneity of microbial signatures remains insufficiently defined. This study investigated disease-associated intestinal microbiome profiles and ecological patterns in patients with adenoma(s) or CRC at different anatomic sites. From 32 healthy, 30 adenoma, and 31 CRC patients, 690 stool, colonic aspirate, and mucosal biopsy samples were prospectively collected. CRC-related alterations were observed in fecal and mucosal microbiomes. Left- versus right-sided neoplastic lesions differed in mucosal metacommunity composition; right-sided CRC displayed an elevated inter-phylum ecological network, whereas left-sided CRC showed enriched Fusobacterium. Rectal neoplasia harbored a tumor microbiome distinct from other anatomic tumor sites, suggesting heterogeneous host–microbe ecological relationships that may shape tumor microenvironment differences.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Abstract

Objective, Methods, Results, Conclusion

Introduction

Study design and sample collection workflow

Cancer Biol Med 2026. doi: 10.20892/j.issn.2095-3941.2025.0846 ORIGINAL ARTICLE Comprehensive microbiome profiling reveals mucosal microbiome heterogeneity in patients with left-and right-sided colorectal neoplasia Sunny H. Wong 1,2, Thomas N.Y. Kwong3, Ru Zhang3,4, Thomas Y.T. Lam5, Andrew M.Y. Ho3, Wing Wah Leung6, Xing Kang 1,3, Harry C. H. Lau3, Eagle S. H. Chu3, Marc T. L. Wong3, Louis H. S. Lau3, Rashid N. S. Lui3, Raymond S.Y. Tang3, James Y.W. Lau6, Simon S. M. Ng6, Jun Yu3,7, Joseph J.Y. Sung 1,2 1Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; 2 Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, National Healthcare Group, Singapore 308433, Singapore; 3 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; 4Shenzhen People’s Hospital, Shenzhen 518020, China; 5The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; 6 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; 7CUHK-Shenzhen Research Institute, Shenzhen 518057, China | 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. | | --- | --- | | KEYWORDS | 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.
Colorectal cancer; colorectal adenomas; colon carcinogenesis; colonic microflora; gut microbiome | Introduction Colorectal cancer (CRC) is a significant global health burden1. The development of CRC is a complex process that is influenced by genetic and environmental factors. Recent studies have highlighted the importance of the gut microbiome in the Correspondence to: Joseph J.Y. Sung [E-mail: josephsung@ntu.edu.sg](E-mail: josephsung@ntu.edu.sg) ORCID ID: [https://orcid.org/0000-0003-3125-5199](https://orcid.org/0000-0003-3125-5199) Received January 8, 2026; accepted March 25, 2026; published online May 26, 2026. Available [at www.cancerbiomed.org](at www.cancerbiomed.org) ©2026 The Authors. Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4 .0) pathogenesis of CRC. The CRC microbiome exhibits a significant compositional shift compared to the microbiome in healthy individuals with certain bacteria, such asFusobacterium nucleatum, Bacteroides fragilis, and Peptostreptococcus anaero bius, implicated in tumor development and progression. It is well-established that different subtypes of CRC preferentially arise at dif

FAQs

What was the study purpose regarding microbiomes in colorectal neoplasia?

To investigate profiles and ecological patterns of disease-associated intestinal microbiome across different anatomic locations in patients with adenoma(s) or CRC.

How many samples and participants were included in the study?

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

What microbiome differences were observed between left- and right-sided CRC?

Mucosal microbiome composition differed by metacommunities: right-sided CRC showed an elevated inter-phylum ecological network, while left-sided CRC had enriched abundance of Fusobacterium.

Sep 22, 2026

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