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The current approach for treating pancreatic cancer involves locoregional control with surgical resection and systemic therapy in the form of cytotoxic chemotherapy. However, despite standard-of-care treatment, the outcomes remain dismal. Emerging evidence suggests that the gut microbiota plays a significant role in pancreatic carcinogenesis through dysbiosis, chronic inflammation and immune modulation. Dysbiosis-driven alterations in the gut microbiota composition can disrupt intestinal homeostasis, promote systemic inflammation and create a tumor-permissive microenvironment in the pancreas. Moreover, the gut microbiota modulates the efficacy of systemic therapies, including chemotherapy and immunotherapy, by impacting drug metabolism and shaping the tumor immune landscape. This review is mainly focused on exploring the intricate interplay between the gut microbiota and pancreatic cancer, and also highlighting its dual role in carcinogenesis and the therapeutic response.<\/jats:p>","DOI":"10.3390\/ijms26073112","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:11:40Z","timestamp":1743135100000},"page":"3112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["From Microbiome to Malignancy: Unveiling the Gut Microbiome Dynamics in Pancreatic Carcinogenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-5499","authenticated-orcid":false,"given":"Dhanisha","family":"Sulekha Suresh","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, BDB 573 1808 7th Avenue South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1886-685X","authenticated-orcid":false,"given":"Tejeshwar","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, BDB 573 1808 7th Avenue South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivaan","family":"Dudeja","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, BDB 573 1808 7th Avenue South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Iyer","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, BDB 573 1808 7th Avenue South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Dudeja","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, BDB 573 1808 7th Avenue South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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