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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 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\nUniversity of Florida, United States  \nREVIEWED BY  \nMiguel Carda Die´guez,  \nFundacio´n para el Fomento de la Investigacio´ n Sanitaria y Biome´ dica de la Comunitat Valenciana (FISABIO), Spain Tae Il Kim,  \nYonsei University, Republic of Korea Daniel Commane,  \nNorthumbria University, United Kingdom  \n*CORRESPONDENCE  \nMingyu Sun  \n [mysun248@hotmail.com](mysun248@hotmail.com)  \nRECEIVED 09 June 2026  \nREVISED 05 August 2026  \nACCEPTED 24 August 2026  \nPUBLISHED 04 September 2026  \nCITATION  \nYu 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.  \nFront. Cell. Infect. Microbiol. 16:1904188 .  \ndoi: 10.3389/fcimb.2026.1904188  \nCOPYRIGHT  \n© 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.  \nSpatial niches of the colorectal cancer microbiome: differences, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota  \nMinghui 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*  \n1Shuguang 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  \nColorectal 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.  \nKEYWORDS  \ncolorectal cancer, fecal microbiota, gut microbiome, intratumoral microbiota, mucosal microbiota, non-invasive screening, precision medicine, spatial niche  \n1 Introduction  \nColorectal 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","cbCaiaQem1ZqFHbG","https://ap.wps.com/l/cbCaiaQem1ZqFHbG","pdf",3293080,16,"English","# Introduction\n## Specimen-type heterogeneity and reproducibility challenges\n## Spatial organization of the gut microbiota\n## Fecal specimens: strengths and limitations","[{\"question\":\"Why do CRC microbiome studies show inconsistent and hard-to-reproduce results?\",\"answer\":\"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.\"},{\"question\":\"What distinct sample niches does the review focus on?\",\"answer\":\"The review compares and contrasts fecal, mucosal, and intratumoral microbiota during CRC progression, emphasizing differences, formation mechanisms, and interrelationships.\"},{\"question\":\"What model does the review propose for spatial niches of the CRC microbiome?\",\"answer\":\"It proposes a “seed bank–colonizers–specialized populations” model to describe a continuous but non-equivalent hierarchy among these niches.\"}]","Spatial niches of the colorectal cancer microbiome - differences, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota | PDF",1790114160]