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Microbiol."],"abstract":"<jats:p>Digestive system malignant tumors (DSMTs)\u2014including gastric, pancreatic, colorectal, liver, and esophageal cancers\u2014are major contributors to cancer-related deaths worldwide, owing to their increasing incidence and poor prognoses. Improving patient survival hinges on a deeper understanding of the mechanisms driving DSMT initiation, progression, and therapeutic resistance. This review offers a novel perspective by exploring DSMTs through the lens of the emerging concept of intratumoral microbiota. We outline the historical context and diverse origins of intratumoral microbiota, detailing their multifaceted roles in DSMTs pathogenesis. Additionally, we highlight innovative traditional Chinese medicine strategies that modulate the intratumoral microecosystem for DSMTs prevention and therapy. Finally, we critically assess the translational potential and current challenges associated with microbiota-targeted anticancer therapeutics. Adopting a microbiota-centric paradigm opens new avenues for next-generation precision oncology, aiming to improve outcomes for patients with DSMTs.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1829524","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:39:56Z","timestamp":1781069996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering intratumoral microbiota in digestive system tumors: mechanisms and emerging therapeutic strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Huamin","family":"Zeng","sequence":"first","affiliation":[{"name":"Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People\u2019s Hospital (The Second Clinical Medical College, Affiliated Fifth People\u2019s Hospital of Chengdu University of Traditional Chinese Medicine)","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]},{"name":"College of Medical Technology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People\u2019s Hospital (The Second Clinical Medical College, Affiliated Fifth People\u2019s Hospital of Chengdu University of Traditional Chinese Medicine)","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.ccell.2022.01.003","article-title":"Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer","volume":"40","author":"Alam","year":"2022","journal-title":"Cancer Cell."},{"key":"B2","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1158\/2326-6066.cir-20-0877","article-title":"Gut microbiota and antitumor immunity: potential mechanisms for clinical effect","volume":"9","author":"Baruch","year":"2021","journal-title":"Cancer Immunol. 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