{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:41:03Z","timestamp":1776336063027,"version":"3.51.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"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. Immunol."],"abstract":"<jats:p>Fibroblast growth factor (FGF)\u2013fibroblast growth factor receptor (FGFR) signaling constitutes a fundamental regulatory network governing epithelial turnover, metabolic homeostasis, and immune modulation across the gastrointestinal tract. Although discrete FGF pathways have been intensively investigated in inflammatory bowel disease, hepatobiliary disorders, and gastrointestinal malignancies, how these signaling programs are coordinated across pathological contexts remains insufficiently resolved. In this review, we integrate evidence from human cohorts, experimental systems, and clinical studies to conceptualize the FGF\u2013FGFR axis as a context-dependent metabolic-barrier-immune rheostat. Paracrine activation of epithelial FGFR2b supports mucosal restitution and barrier re-establishment following injury, whereas endocrine FGFs\u2014including FGF19, FGF21, and FGF23\u2014couple bile acid signaling, systemic metabolic stress, and mineral balance to intestinal and hepatic inflammatory responses. Perturbation of these adaptive signaling circuits contributes to persistent inflammation and is frequently co-opted by oncogenic events, such as FGFR2b amplification, FGFR2 gene fusions, and aberrant FGF19\u2013FGFR4 activation, during gastrointestinal tumorigenesis. Framing the FGF\u2013FGFR network as an integrated rheostat offers a unifying mechanistic paradigm that links epithelial damage, metabolic dysregulation, and cancer development. It underscores the need for context-selective therapeutic interventions that reconcile tissue repair with long-term oncogenic risk.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1805290","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T11:00:37Z","timestamp":1774522837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The FGF\u2013FGFR axis as an immune\u2013metabolic rheostat in gastrointestinal inflammation and cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Khamis Salem Saeed","family":"Saad","sequence":"first","affiliation":[{"name":"Institute of Deigestive Diseases, Renmin Hospital, Hubei University of Medicine","place":["Shiyan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Renmin Hospital, Hubei University of 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