{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:23:50Z","timestamp":1787318630008,"version":"build-2736575974"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"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":["Oncol. Rev."],"abstract":"<jats:p>Chemotherapy-induced gastrointestinal toxicity (CIGT) is a common, dose-limiting complication of cancer therapy that manifests as mucositis, nausea, vomiting, diarrhea, abdominal pain, and weight loss. Epithelial injury, barrier disruption, oxidative stress, and inflammatory signaling are well-established features of CIGT affecting the mucosa, however, these mechanisms do not fully explain the persistence of neurosensory symptoms that can outlast histologic recovery. In particular, the pathways linking epithelial damage to sustained activation of enteric and extrinsic sensory circuits remain incompletely defined. Here, we propose that CIGT involves coordinated interactions between the injured intestinal epithelium and peripheral neural pathways, in which epithelial-derived signals and inflammatory mediators drive neuronal hyperexcitability and sustained sensory dysfunction. Serotonergic signaling from enterochromaffin cells represents a well-established mechanism linking epithelial activity to vagal afferents and nausea. In contrast, the contributions of inflammatory mediators, oxidative stress, barrier dysfunction, and microbial dysbiosis to enteric and dorsal root ganglion (DRG) neuron sensitization remains less clearly defined. Current clinical management is largely palliative and targets downstream symptoms rather than upstream epithelial-to-neural interactions. A better understanding of how epithelial injury engages neural pathways may enable mechanism-based therapies that improve symptom control, preserve treatment intensity, and enhance patient outcomes.<\/jats:p>","DOI":"10.3389\/or.2026.1814601","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:30:41Z","timestamp":1778477441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The mucosal-neural axis in chemotherapy-induced gastrointestinal toxicity"],"prefix":"10.3389","volume":"20","author":[{"given":"Mikaela R.","family":"Nemani","sequence":"first","affiliation":[{"name":"Department of Biology, University of Miami","place":["Coral Gables, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Rieger","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Miami","place":["Coral Gables, FL, United 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