Spatial niches of the colorectal cancer microbiome - differences, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota

Sep 22, 2026

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Colorectal cancer (CRC) is a leading global malignancy and a major cause of cancer-related death. Gut microbiome research draws attention for roles in CRC initiation, progression, early detection, prognosis, and therapy response, yet findings remain inconsistent with limited reproducibility across studies. This review attributes part of the problem to differences in specimen type and proposes a spatial-niche framework comparing fecal, mucosal, and intratumoral microbiota to improve mechanistic interpretation and clinical translation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Specimen-type heterogeneity and reproducibility challenges

Spatial organization of the gut microbiota

Fecal specimens: strengths and limitations

TYPE Review PUBLISHED 04 September 2026 DOI 10.3389/fcimb.2026.1904188 OPEN ACCESS EDITED BY Ye Yang, University of Florida, United States REVIEWED BY Miguel Carda Die´guez, Fundacio´n para el Fomento de la Investigacio´ n Sanitaria y Biome´ dica de la Comunitat Valenciana (FISABIO), Spain Tae Il Kim, Yonsei University, Republic of Korea Daniel Commane, Northumbria University, United Kingdom *CORRESPONDENCE Mingyu Sun [mysun248@hotmail.com](mysun248@hotmail.com) RECEIVED 09 June 2026 REVISED 05 August 2026 ACCEPTED 24 August 2026 PUBLISHED 04 September 2026 CITATION Yu M, Shi X, Li D, Li Y and Sun M (2026) Spatial niches of the colorectal cancer microbiome: differences, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota. Front. Cell. Infect. Microbiol. 16:1904188 . doi: 10.3389/fcimb.2026.1904188 COPYRIGHT © 2026 Yu, Shi, Li, Li and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Spatial niches of the colorectal cancer microbiome: differences, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota Minghui Yu 1,2,3, Xin Shi 1,2,3, Dong Li 1,2,3, Yuelin Li 1,2,3 and Mingyu Sun 1,2,3* 1Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 2Shanghai University of Traditional Chinese Medicine, Shanghai, China, 3 Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China Colorectal cancer (CRC) is one of the most common malignancies worldwide anda leading cause of cancer-related mortality. The gut microbiome has attracted growing attention because of its involvement in CRC initiation and progression, early detection, prognostic evaluation, and therapeutic response. However, CRC microbiome studies continue to face inconsistent ﬁndings and limited reproducibility, partly because of differences in specimen type. Directly comparing microbial signals from fecal, mucosal, and intratumoral samples may therefore bias mechanistic interpretation and mislead clinical translation. From a spatial-niche perspective, this review summarizes the distinct characteristics, formation mechanisms, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota during CRC progression. We further propose a “seed bank–colonizers–specialized populations” model to conceptualize the continuous but non-equivalent hierarchy among these niches. By providing a clearer spatially stratiﬁed framework, this review aims to help move CRC microbiome research beyond descriptive associations toward precision-oriented applications supported by mechanistic interpretability, reproducible evidence, and clinical translatability. KEYWORDS colorectal cancer, fecal microbiota, gut microbiome, intratumoral microbiota, mucosal microbiota, non-invasive screening, precision medicine, spatial niche 1 Introduction Colorectal cancer (CRC) remains one of the most burdensome malignancies worldwide. According to GLOBOCAN 2022 global cancer statistics, CRC ranks among the leading causes of cancer incidence and mortality worldwide and continues to impose a substantial burden on public health systems (Bray et al., 2024). The rising incidence of early-onset CRC and the increasingly evident shift toward younger age at diagnosis have become major global public health concerns (Siegel et al., 2019; Sinicrope, 2022) . The gut microbiome has attracted considerable attention because of its involve

FAQs

Why do CRC microbiome studies show inconsistent and hard-to-reproduce results?

A major contributor is heterogeneity in specimen types across studies, including fecal, mucosal biopsy, and intratumoral samples, which can bias mechanistic interpretation and clinical translation.

What distinct sample niches does the review focus on?

The review compares and contrasts fecal, mucosal, and intratumoral microbiota during CRC progression, emphasizing differences, formation mechanisms, and interrelationships.

What model does the review propose for spatial niches of the CRC microbiome?

It proposes a “seed bank–colonizers–specialized populations” model to describe a continuous but non-equivalent hierarchy among these niches.

Sep 22, 2026

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