{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:36:56Z","timestamp":1787618216820,"version":"build-2736575974"},"reference-count":170,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Colon cancer (CC) exhibits substantial heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) in terms of embryological origin, molecular characteristics, immune microenvironment, and therapeutic response. Increasing evidence suggests that spatial heterogeneity of the gut microbiota may contribute to these site-specific differences through interactions with local immune, inflammatory, and metabolic microenvironments. Recent studies have also indicated that gut microbiota dysbiosis may participate in the progression, therapeutic response, and microenvironmental remodeling of CC. This review summarizes current evidence regarding the role of gut microbiota spatial heterogeneity in RCC and LCC, with particular emphasis on its potential associations with molecular features, immune regulation, and local metabolic alterations. Furthermore, we discuss recent advances in Traditional Chinese Medicine (TCM)-based interventions targeting the gut microbiota in CC, including potential links between common TCM syndromes, microbial dysbiosis, mucosal barrier dysfunction, and immune-inflammatory alterations. We also summarize the regulatory effects of representative botanical monomers and classical TCM formulas on microbial homeostasis and tumor-related microenvironmental changes. Importantly, this review does not aim to establish fixed correspondences between specific TCM syndromes and tumor location. Instead, gut microbiota heterogeneity may serve as a modern biological reference for understanding site-specific pathogenesis and guiding individualized TCM interventions in CC.<\/jats:p>","DOI":"10.3389\/fphar.2026.1768252","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:42:23Z","timestamp":1781239343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiota regulation and Traditional Chinese Medicine syndrome differentiation in right- and left-sided colon cancer heterogeneity \u2014 A review"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiatian","family":"Chen","sequence":"first","affiliation":[{"name":"Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinting","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3390\/diagnostics15020142","article-title":"KRAS, NRAS, and BRAF hot-spot mutations in relation to sidedness of primary colorectal cancer: a retrospective cohort study","volume":"15","author":"Abdelgadir","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2655193","DOI":"10.1080\/19490976.2026.2655193","article-title":"The distinct roles of Negativicoccus and Fusobacterium in proximal- and late-onset colorectal cancer","volume":"18","author":"Ali","year":"2026","journal-title":"Gut Microbes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3389\/fnbeh.2018.00141","article-title":"Alterations of the innate immune system in susceptibility and resilience after social defeat stress","volume":"12","author":"Ambr\u00e9e","year":"2018","journal-title":"Front. 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