{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:51:47Z","timestamp":1793638307718,"version":"4.5.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"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":"\n Objectives<\/jats:title>\n \n Sepsis-induced acute lung injury (SI-ALI) significantly contributes to sepsis mortality, with CD8\n +<\/jats:sup>\n T cell depletion being a critical pathogenic factor. While\n \n Blautia<\/jats:italic>\n <\/jats:italic>\n , a gut commensal bacterium with established probiotic benefits in diverse diseases, its role in SI-ALI pathogenesis remains undefined. Here, we investigated the therapeutic potential of\n Blautia<\/jats:italic>\n in lethal SI-ALI.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Gut microbiome profiling was performed in SI-ALI patients and healthy controls to identify disease-associated microbial alterations. A cecal ligation and puncture (CLP) rat model of sepsis was used to validate microbiota changes and evaluate the therapeutic effects of\n Blautia<\/jats:italic>\n supplementation. Untargeted metabolomic analysis was conducted to identify key metabolites associated with\n Blautia<\/jats:italic>\n . Functional studies were performed to assess lung injury, immune responses, CD8\n +<\/jats:sup>\n T cell abundance, and survival following\n Blautia<\/jats:italic>\n or metabolite administration.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Gut microbiome analysis identified significant\n Blautia<\/jats:italic>\n depletion in SI-ALI patients compared to healthy controls. This pathogenic alteration was faithfully reproduced in cecal ligation and puncture (CLP) -modeled septic rats, in which\n Blautia<\/jats:italic>\n supplementation attenuated lung injury, enhanced systemic immune responses,and improved survival. Untargeted metabolomic profiling identified indole-3-acetic acid (IAA) as a key\n Blautia<\/jats:italic>\n -derived metabolite. Administration of IAA alone recapitulated the protective effects of\n Blautia<\/jats:italic>\n , significantly ameliorating SI-ALI. Crucially, both interventions restored CD8\n +<\/jats:sup>\n T cell populations and augmented their functional responses. Clinical analysis revealed that elevated\n Blautia<\/jats:italic>\n abundance in sepsis patients inversely correlated with pulmonary injury severity and positively associated with augmented CD8\n +<\/jats:sup>\n T cell effector functions.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n Our findings establish that\n Blautia<\/jats:italic>\n and\n Blautia<\/jats:italic>\n -derived IAA mitigates SI-ALI by counteracting CD8\n +<\/jats:sup>\n T cell depletion and dysfunction, highlighting a novel and promising mechanism-based therapeutic strategy for life-threatening sepsis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1707493","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:21:22Z","timestamp":1774243282000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Indole-3-acetic acid derived from Blautia protects against sepsis-induced acute lung injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Ke","family":"Chao","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Ding","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Ji","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Medicine, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilong","family":"Sun","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfu","family":"Yang","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.04.001","article-title":"Sepsis: current dogma and new perspectives","volume":"40","author":"Deutschman","year":"2014","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1001\/jama.2017.17687","article-title":"Enhancing recovery from sepsis: A review","volume":"319","author":"Prescott","year":"2018","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat Rev Nephrol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"6737","DOI":"10.1038\/s41467-024-51209-9","article-title":"Gut-derived memory \u03b3\u03b4 T17 cells 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