{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:10:06Z","timestamp":1793059806626,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371177"],"award-info":[{"award-number":["32371177"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation Project of Chongqing","award":["CSTB2022NSCQ-LZX0017"],"award-info":[{"award-number":["CSTB2022NSCQ-LZX0017"]}]},{"name":"Chongqing Medical University 2024 Graduate Top Talent Cultivation Program","award":["BJRC202419"],"award-info":[{"award-number":["BJRC202419"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:p>\n                    The gut\u2013lung axis is involved in acute lung injury (ALI) and its fatal sequela, acute respiratory distress syndrome (ARDS), yet the molecular mechanisms governing this crosstalk remain poorly defined. Untargeted metabolomics of plasma revealed significant dysregulation of tryptophan metabolism in ARDS patients compared to healthy controls. Murine dietary interventions demonstrated that high tryptophan intake alleviated ALI severity, whereas deficiency exacerbated injury, with protection being gut microbiota dependent. 16S ribosomal RNA (16S rRNA) gene sequencing revealed marked depletion of a functionally central bacterium\n                    <jats:italic toggle=\"yes\">Lactobacillus johnsonii<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">L. johnsonii<\/jats:italic>\n                    ) during ALI. Supplementation with\n                    <jats:italic toggle=\"yes\">L. johnsonii<\/jats:italic>\n                    or its encapsulated form attenuated ALI, but this required dietary tryptophan sufficiency. Mechanistically,\n                    <jats:italic toggle=\"yes\">L. johnsonii<\/jats:italic>\n                    converts tryptophan into oxindole, which enters pulmonary macrophages, promotes the aryl hydrocarbon receptor-RelA binding, and thereby suppresses RelA-mediated transcriptional activation of C-X-C motif chemokine 13 (CXCL13). Both genetic ablation and pharmacological inhibition of CXCL13 ameliorated ALI symptoms. Importantly, oxindole and CXCL13 levels correlated with ARDS severity in patients, suggesting their clinical relevance. Collectively, these findings define a protective microbiota-dependent gut\u2013lung axis in ALI\/ARDS that is mediated by dietary tryptophan-derived oxindole, which acts at least partially through CXCL13 suppression to underscore targetable diet\u2013microbe\u2013metabolite therapeutic paradigms.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519332123","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:38:07Z","timestamp":1772213887000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Microbial metabolite oxindole curbs acute lung injury by suppressing CXCL13"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0695-0968","authenticated-orcid":false,"given":"Shixin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1785-4603","authenticated-orcid":false,"given":"Zhenghai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency, The University-Town Hospital of Chongqing Medical University","place":["Chongqing, 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Medicine, The First Affiliated Hospital of Chongqing Medical University, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2585-4494","authenticated-orcid":false,"given":"Dandan","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Emergency, The University-Town Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Basic Medicine Research and Innovation Center 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