{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:10:50Z","timestamp":1792624250263,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172129"],"award-info":[{"award-number":["82172129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Neutrophil elastase (NE) is associated with sepsis occurrence and progression. We hypothesized that the NE inhibitor Sivelestat might modulate abnormal gut microbiota and metabolites during sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty Sprague-Dawley (SD) rats were randomly divided into sham control (SC), sepsis (CLP), and sepsis+Sivelestat (Sive) groups. The rats\u2019 survival status was monitored for 24 hours postoperatively, and feces were collected for microbiome and non-targeted metabolomics analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sivelestat administration significantly improved the survival of septic rats (80% vs 50%, <jats:italic>P<\/jats:italic> = 0.047). Microbiome analysis showed that the microbiota composition of rats in the CLP group was significantly disturbed, as potential pathogens such as <jats:italic>Escherichia-Shigella<\/jats:italic> and <jats:italic>Gammaproteobacteria<\/jats:italic> became dominant, and the beneficial microbiota represented by <jats:italic>Lactobacillus<\/jats:italic> decreased. These changes were reversed in Sive group, and the overall microbial status was restored to a similar composition to SC group. Differential analysis identified 36 differential operational taxonomic units and 11 metabolites between the Sive and CLP groups, such as 6-Aminopenicillanic acid, gamma-Glutamyl-leucine, and cortisone (variable importance in projection&amp;gt;1and <jats:italic>P<\/jats:italic>&amp;lt;0.05). These discriminatory metabolites were highly correlated with each other and mainly involved in the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Integrated microbiome and metabolome analyses found that almost all Sivelestat-modulated microbes were associated with differential metabolites (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), such as <jats:italic>Lactobacillu<\/jats:italic>s and some amino acids, suggesting that the Sivelestat-induced metabolic profile differences were in part due to its influence on the gut microbiome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sivelestat administration in septic rats improved survival, gut microbiota composition and associated metabolites, which could provide new options for sepsis treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2022.818391","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T09:13:33Z","timestamp":1647335613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Positive Effects of Neutrophil Elastase Inhibitor (Sivelestat) on Gut Microbiome and Metabolite Profiles of Septic Rats"],"prefix":"10.3389","volume":"12","author":[{"given":"Yali","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huoyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongwen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13054-020-02989-1","article-title":"The Gut Microbiome's Role in the Development, Maintenance, and Outcomes of Sepsis","volume":"24","author":"Adelman","year":"2020","journal-title":"Crit. 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