{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:16:22Z","timestamp":1788509782272,"version":"build-2803163510"},"reference-count":113,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"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>Radiation-induced injury is a complex pathological process involving DNA damage, oxidative stress, inflammatory amplification, epithelial barrier disruption, immune dysregulation, metabolic remodeling, and impaired tissue repair. Accumulating evidence indicates that the gut microbiota is not merely altered by irradiation but may also modify host radiation responses and tissue recovery; however, direct causal support remains confined to selected microbes, metabolites, and pathways, predominantly in preclinical models. Irradiation is frequently associated with reduced microbial diversity, depletion of selected commensals, expansion of opportunistic pathobionts, and altered microbial metabolic output; selected experimental studies further indicate that these changes can modify intestinal injury and host recovery. Conversely, defined microbes and metabolites have improved radiation outcomes in preclinical intervention models by supporting epithelial, immune, and metabolic homeostasis. In this review, we summarize current advances in understanding the gut microbiota\u2013metabolite axis in radiation-induced injury. We first discuss radiation-induced gut dysbiosis and the major microbial metabolites involved, including short-chain fatty acids, tryptophan-derived metabolites, bile acids, lipid metabolites, polyamines, and other bioactive molecules. We then highlight the key mechanisms by which gut microbiota and microbial metabolites mitigate radiation injury, including suppression of oxidative stress, inhibition of inflammatory signaling, restoration of epithelial barrier integrity, promotion of intestinal stem cell-mediated regeneration, regulation of immune homeostasis, and modulation of lipid peroxidation-associated ferroptosis. Finally, we evaluate microbiota-targeted intervention strategies, including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, antibiotic modulation, natural products, engineered probiotics, and nanomedicine-assisted delivery systems. Overall, the gut microbiota\u2013metabolite axis represents a biologically plausible and increasingly testable target for radioprotection and mitigation, although its clinical utility remains to be established. Future studies should move beyond descriptive microbiome profiling toward causal, function-oriented, and multi-omics-driven investigations, with particular emphasis on the microbiota\u2013lipid metabolism\u2013ferroptosis axis and precision microbiome therapeutics. Carefully validated microbiota-targeted approaches may provide future opportunities to reduce normal-tissue toxicity and improve recovery without compromising tumor control.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1923929","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:53:33Z","timestamp":1788508413000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota and microbiota-derived metabolites in radiation-induced injury: mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiyan","family":"Zou","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]},{"name":"Sichuan Provincial Engineering Research Center of Nuclear Medical Equipment Translation and Application, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyun","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Life Science and Engineering, Southwest University of Science and Technology","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature12331","article-title":"Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota","volume":"500","author":"Atarashi","year":"2013","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nature25432","article-title":"Chromosomal instability drives metastasis through a cytosolic DNA response","volume":"553","author":"Bakhoum","year":"2018","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation","volume":"421","author":"Bakkenist","year":"2003","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nature06196","article-title":"Identification of stem cells in small intestine and colon by marker gene Lgr5","volume":"449","author":"Barker","year":"2007","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41577-023-00951-0","article-title":"Role of the microbiota in response to and recovery from cancer therapy","volume":"24","author":"Blake","year":"2024","journal-title":"Nat. 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