{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:44:50Z","timestamp":1788583490888,"version":"build-2803163510"},"reference-count":62,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Sailing Program","award":["23YF1405000"],"award-info":[{"award-number":["23YF1405000"]}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2023ZDFC0101"],"award-info":[{"award-number":["2023ZDFC0101"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology of Shanghai Committee","award":["23Y31900100"],"award-info":[{"award-number":["23Y31900100"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272198"],"award-info":[{"award-number":["82272198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. This study aims to explore the role of gut microbiota components in regulating CX3CR1 expression and its impact on pneumonia-induced lung injury during sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1+ NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1+ NK cells and interferon (IFN)-\u03b3 secretion, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K\/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1+ NK cells via the PI3K\/AKT pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/burnst\/tkaf069","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:46:58Z","timestamp":1761655618000},"source":"Crossref","is-referenced-by-count":3,"title":["Gut microbiota metabolite butyric acid alleviated\n                    <i>Klebsiella Pneumoniae<\/i>\n                    induced lung injury by regulating CX3CR1+NK via PI3K\/AKT pathway"],"prefix":"10.1093","volume":"14","author":[{"given":"Sucheng","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-8468","authenticated-orcid":false,"given":"Meijia","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Zhongshan Hospital, Fudan University , 38 Yixueyuan Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqi","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Ministry of Science and Technology Key Laboratory of Health and Disease Genomics, National Health Commission Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies , 2140 Xietu Road, Shanghai 200237 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenju","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Zhongshan Hospital, Fudan University , 38 Yixueyuan Road, Shanghai 200032 ,","place":["China"]},{"name":"Shanghai Key Laboratory of Lung Inflammation and Injury , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]},{"name":"Institute of Emergency Rescue and Critical Care, Fudan University , 138 Yixueyuan Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"2026013104265847400_ref1","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1056\/NEJMclde1815472","article-title":"Sepsis 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