{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:56:33Z","timestamp":1790200593538,"version":"4.1.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"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>The significant bidirectional comorbidity risk and extensive subclinical involvement observed between chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) underscore the pivotal role of the \u201cgut-lung axis\u201d in cross-organ pathological crosstalk. Here, we comprehensively review the molecular and immunological mechanisms driving this comorbidity. Genome-wide association studies (GWAS) have substantiated genetic pleiotropy that underpins a shared susceptibility to mucosal defense deficits. The \u201ccommon mucosal immune system\u201d (CMIS), rooted in embryonic homology, constitutes the anatomical basis for this pathological interplay, wherein aberrant immune cell homing, Th17\/Treg imbalance, and the cross-organ trafficking of innate lymphoid cells (ILCs) mediate the distal dissemination of inflammation. Furthermore, gut dysbiosis-induced depletion of short-chain fatty acids (SCFAs), acting in concert with systemic hypoxia and the IL-23\/IL-17 axis, potentiates synergistic injury to the gut-lung barriers. We highlight the reciprocal, bidirectional causality of this \u201chypoxic loop\u201d and its testable mechanistic predictions for barrier dysfunction. Furthermore, we evaluate pharmacological evidence from drug repositioning, alongside a critical examination of the \u201chidden axis\u201d of clinical therapies as profound iatrogenic confounders. Elucidating these mechanisms is critical for establishing systemic diagnostic and therapeutic strategies; interventions targeting shared molecular targets and the microbiota hold promise for achieving a simultaneous treatment approach for these distinct pathologies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1796944","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:48:09Z","timestamp":1776836889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The gut-lung axis: pathological crosstalk and inter-organ communication in chronic obstructive pulmonary disease and inflammatory bowel disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinying","family":"Liu","sequence":"first","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Yan","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Yang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"National Clinical Research Center for Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-0584","article-title":"Disturbed intestinal integrity in patients with copd: Effects of 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