{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:06:37Z","timestamp":1790377597483,"version":"4.1.0"},"reference-count":331,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hellenic Foundation for Research and Innovation (HFRI) under the 5th Call for HFRI PhD Fellowships","award":["19292"],"award-info":[{"award-number":["19292"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastrointestinal (GI) cancers represent a major global health burden. Among them, colorectal cancer (CRC) is the most common type, followed by esophagus, stomach, liver, and pancreatic cancer. Since disturbance of the gut microbiota has been directly associated with the development of severe health issues, including cancer, probiotic administration may induce dysbiosis reversion and ameliorate carcinogenesis. Therefore, manipulation of the gut microbiota composition based on probiotic utilization has gradually attained scientific interest as a potent therapeutic modality for GI cancers. This review aims to synthesize the current in vitro and in vivo evidence on probiotics\u2019 effectiveness in GI cancer chemoprevention and treatment. It also provides a classification of the fundamental anticancer features of probiotics, including antiproliferation and cell death induction, anticarcinogenic compound production, reduction in chemotherapy-related toxicity, gut microbiota modulation, intestinal barrier improvement, antioxidant activity, immunomodulatory\/anti-inflammatory effects, and carcinogen detoxification. Finally, it underscores the future perspectives and challenges of probiotic administration to individuals. In this regard, it emphasizes the exploitation of advanced encapsulation techniques and the development of novel genetically engineered probiotics and next-generation probiotics as feasible ways to improve their bioavailability, ensure their targeted delivery, and eliminate their mild side effects to the host\u2019s health.<\/jats:p>","DOI":"10.3390\/ijms26167857","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:44:21Z","timestamp":1755186261000},"page":"7857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular Mechanisms of Probiotic Action Against Gastrointestinal Cancers"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0514-7170","authenticated-orcid":false,"given":"Christina","family":"Thoda","sequence":"first","affiliation":[{"name":"Laboratory of General Microbiology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki (A.U.TH.), 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-5205","authenticated-orcid":false,"given":"Maria","family":"Touraki","sequence":"additional","affiliation":[{"name":"Laboratory of General Microbiology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki (A.U.TH.), 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/s43018-023-00602-2","article-title":"Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation","volume":"4","author":"Queen","year":"2023","journal-title":"Nat. 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