{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:45:36Z","timestamp":1792521936529,"version":"4.5.0"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"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>\n                    Radiation-induced lung injury (RILI) constrains thoracic radiotherapy dosing and includes acute radiation pneumonitis (RP) and chronic radiation-induced pulmonary fibrosis (RPF). This narrative review explores the gut\u2013lung microbiota axis in RILI, synthesizing evidence from preclinical models, clinical cohorts (N\u00a0=\u00a052\u201389), and randomized controlled trials (RCTs). Radiotherapy induces gut dysbiosis, barrier breakdown, and metabolite changes [e.g., short-chain fatty acid (SCFA) and desaminotyrosine (DAT) depletion], promoting inflammation and fibrosis via pathways such as Toll-like receptor 4\/nuclear factor kappa B (TLR4\/NF-\u03baB), TGF-\u03b2\/Smad, sphingosine-1-phosphate (S1P)\u2013S1PR, and cGAS\u2013STING in animal studies. Inter-species microbial variations hinder translation, while lung microbiota shifts remain nascent. In non-small cell lung cancer cohorts, lower gut microbiota stability (a marker of dysbiosis) is associated with an increased risk of grade \u22652 RP (multivariable-adjusted models, p &amp;lt; 0.05), with higher baseline\n                    <jats:italic>Faecalibacterium<\/jats:italic>\n                    abundance conferring protection; however, causality remains unproven due to antibiotic confounding. Mechanisms involve lipopolysaccharide (LPS) translocation, interleukin 25 (IL-25)\/S1P-driven type 2 innate lymphoid cell (ILC2) migration, regulatory T cell\/T helper 17 cell (Treg\/Th17) imbalance, and extracellular vesicle (EV) signaling, with biomarkers such as 16S rRNA sequencing and EV-miRNAs (e.g., miR-486-5p). Artificial intelligence models predict RP with 75% accuracy. Phase-specific interventions, such as pre-radiotherapy gut microbiota monitoring, intra-radiotherapy SCFA supplementation, subacute DAT modulation, and RPF-targeted EV therapies, have been explored in preliminary pilot studies [for example, one small study reported approximately 12% FEV1 improvement following fecal microbiota transplantation (FMT)]. Future large-scale, stratified RCTs that properly account for antibiotics, chemotherapy, and immunotherapy are required to establish causality beyond the current largely associative clinical evidence. The integration of immunotherapy and proton therapy in such trials may help clarify gut\u2013lung interactions, including any microbiota-preserving effects of proton therapy; the role of the lung microbiota in fibrosis remains preliminary.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1806833","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:25:43Z","timestamp":1782966343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut\u2013lung axis in radiation-induced lung injury: mechanisms and interventions"],"prefix":"10.3389","volume":"17","author":[{"given":"Ping","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Oncology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital)","place":["Qingdao, 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Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengtai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency Internal Medicine, the Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuai","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Emergency Internal Medicine, the Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104461","article-title":"Pathogenic mechanisms and latest therapeutic approaches for radiation-induced lung injury: A narrative 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