{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T19:52:39Z","timestamp":1794253959747,"version":"4.9.0"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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. Microbiol."],"abstract":"<jats:p>\n                    Colorectal cancer (CRC) arises from a multifaceted interplay among the intestinal microbiota, chronic inflammation, and host genomic instability, with microbial dysbiosis serving as an active driver rather than a by-product of malignant transformation. Genotoxic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (colibactin-positive), enterotoxigenic\n                    <jats:italic>Bacteroides fragilis<\/jats:italic>\n                    , and\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    contribute to distinct stages of CRC progression by engaging the DNA-damage response and activating \u03b2-catenin\u2013dependent Wnt signaling and NF-\u03baB\/STAT3 transcriptional programs controlling pro-inflammatory (\n                    <jats:italic>IL-6, IL-8<\/jats:italic>\n                    ), pro-survival (\n                    <jats:italic>BCL-2, BCL-XL<\/jats:italic>\n                    ), and proliferative (\n                    <jats:italic>MYC, CCND1<\/jats:italic>\n                    ) gene expression.. Here, we propose a tri-axial pathogenic framework in which (i) cyclic dinucleotide\u2013mediated activation of the cGAS\u2013STING pathway engages TBK1\u2013IRF3 and NF-\u03baB signaling, driving type I interferons (\n                    <jats:italic>IFN-<\/jats:italic>\n                    \u03b2) and pro-inflammatory cytokines (\n                    <jats:italic>IL-6, TNF-<\/jats:italic>\n                    \u03b1) that couple microbial genotoxic stress to innate inflammation; (ii) altered microbial metabolites, including indoles and bile acids, reprogram AhR and FXR\/TGR5 signaling; and (iii) crypt-anchored biofilms spatially amplify\n                    <jats:italic>IL-6<\/jats:italic>\n                    leading to activation of STAT3, epigenetic silencing of tumor suppressors, and immune evasion. This review critically synthesizes current evidence supporting these axes and maps them onto CRC molecular subsets and tumor location. Recognition of these integrated microbial-host circuits identifies mechanistically grounded candidates for biomarker development, microbiome-based diagnostics, and targeted interventions to restore microbial and immune equilibrium, thereby providing a refined framework for the molecular classification and precision management of CRC.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1795882","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:41:40Z","timestamp":1780378900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Microbial dysbiosis drives colorectal carcinogenesis via integrated inflammatory, metabolic, and biofilm pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Asma","family":"Bachir","sequence":"first","affiliation":[{"name":"Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa Muayad","family":"Altaie","sequence":"additional","affiliation":[{"name":"Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Center of Excellence for Precision Medicine, Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyad","family":"Bendardaf","sequence":"additional","affiliation":[{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Oncology Unit, University Hospital Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman M.","family":"Talaat","sequence":"additional","affiliation":[{"name":"Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Pathology Department, Faculty of Medicine, Alexandria University","place":["Alexandria, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat","family":"Hamoudi","sequence":"additional","affiliation":[{"name":"Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Center of Excellence for Precision Medicine, Research Institute of Medical and Health Sciences, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Pathology Department, Faculty of Medicine, Alexandria University","place":["Alexandria, Egypt"]},{"name":"BIMAI-Lab, Biomedically Informed Artificial Intelligence Laboratory, University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Division of Surgery and Interventional Science, University College London","place":["London, United Kingdom"]},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"881","DOI":"10.3390\/nu13030881","article-title":"The Western dietary pattern combined with vancomycin-mediated changes to the gut microbiome exacerbates colitis severity and colon tumorigenesis","volume":"13","author":"Aardema","year":"2021","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41571-020-00445-1","article-title":"Rising incidence of early-onset colorectal cancer - a call to action","volume":"18","author":"Akimoto","year":"2021","journal-title":"Nat. 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