{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:10:48Z","timestamp":1790251848725,"version":"4.1.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut-lung axis, the long-range communication between the intestinal microbiota and the lungs, has been shown to influence immunotherapy responses in non-small-cell lung cancer (NSCLC). Existing reviews, however, focus almost exclusively on the chemical signaling dimension of microbial metabolites. The relay function of enteroendocrine hormones and the integrative role of the nervous system have yet to be incorporated into a unified framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched seven databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP) from inception to June 2026 for original studies and reviews addressing gut microbiota and lung-gut-brain axis mechanisms in the context of NSCLC or small-cell lung cancer. Two authors independently performed study selection, data extraction, and thematic classification. A narrative synthesis was conducted, with evidence organized along three signaling axes: soluble metabolites, the metabolic-endocrine axis, and neuroimmune integration. As a narrative review with a systematic search, this study was registered on PROSPERO (CRD420261425826), while formal risk-of-bias assessment and GRADE evaluation were not performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 168 studies was included (only a subset of these included studies cited in the main text). The volume of evidence across the three axes formed a pronounced gradient. Soluble metabolites (short-chain fatty acids, tryptophan metabolites, and bile acids) have been cross-validated in clinical cohorts, animal models, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments; fecal microbiota transplantation and prebiotic strategies have entered clinical trials. The metabolic-endocrine axis rests on a solid foundation in normal physiology, but the key bridging nodes in the NSCLC disease context remain untested. Evidence for the neuroimmune integration axis is the sparsest: the only support for a direct transport function of the vagus nerve comes from a non-peer-reviewed preprint in a non-cancer model, and the full neuroendocrine signal transduction chain remains hypothetical. To address this gap, we outline a pathway model annotated with evidence levels at each node.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Research on the lung-gut-brain axis is heavily concentrated in the chemical dimension. The mechanistic gaps in the endocrine and neural dimensions represent the principal barrier for the field\u2019s transition from correlational description to causal mechanism studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1932225","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:46:36Z","timestamp":1789123596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The lung-gut-brain axis in non-small-cell lung cancer: a narrative review with a systematic search of three signaling pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Yijun","family":"Fan","sequence":"first","affiliation":[{"name":"West China School of Medicine, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Luo","sequence":"additional","affiliation":[{"name":"Out-patient Department, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingrui","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Lung Cancer Center\/Lung Cancer Institute, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aier","family":"Zhou","sequence":"additional","affiliation":[{"name":"West China School of Medicine, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangyu","family":"Liu","sequence":"additional","affiliation":[{"name":"West China School of Medicine, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Quais","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Lung Cancer Center\/Lung Cancer Institute, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faxian","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Lung Cancer Center\/Lung Cancer Institute, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Lung Cancer Center\/Lung Cancer Institute, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: A Cancer J For Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5035371","article-title":"Desired turbulence? 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