{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:44:41Z","timestamp":1792226681945,"version":"4.4.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2022J01728"],"award-info":[{"award-number":["2022J01728"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J01637"],"award-info":[{"award-number":["2023J01637"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Department of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021171","name":"Arts and Science Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ejphar.2025.178229","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:33:10Z","timestamp":1759937590000},"page":"178229","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2\/NLRP3 pathway"],"prefix":"10.1016","volume":"1007","author":[{"given":"Guangwei","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnan","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-013X","authenticated-orcid":false,"given":"Yilang","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-8119","authenticated-orcid":false,"given":"Xiaohong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.178229_bib1","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2019.1707610","article-title":"Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis","volume":"12","author":"Agudelo-Ochoa","year":"2020","journal-title":"Gut Microbes"},{"key":"10.1016\/j.ejphar.2025.178229_bib2","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/s41591-019-0504-5","article-title":"Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice","volume":"25","author":"B\u00e1rcena","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2025.178229_bib3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s43587-021-00093-9","article-title":"Microbiota from young mice counteracts selective age-associated behavioral deficits","volume":"1","author":"Boehme","year":"2021","journal-title":"Nat. Aging."},{"key":"10.1016\/j.ejphar.2025.178229_bib4","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019","volume":"7","year":"2022","journal-title":"Lancet Public Health"},{"key":"10.1016\/j.ejphar.2025.178229_bib5","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1038\/s41380-023-02172-2","article-title":"Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden","volume":"28","author":"Giridharan","year":"2023","journal-title":"Mol. Psychiatr."},{"key":"10.1016\/j.ejphar.2025.178229_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.102165","article-title":"Short-chain fatty acids as modulators of redox signaling in health and disease","volume":"47","author":"Gonz\u00e1lez-Bosch","year":"2021","journal-title":"Redox Biol."},{"key":"10.1016\/j.ejphar.2025.178229_bib7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ijbiomac.2021.03.137","article-title":"Crataegus pinnatifida polysaccharide alleviates colitis via modulation of gut microbiota and SCFAs metabolism","volume":"181","author":"Guo","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejphar.2025.178229_bib8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S2468-1253(16)30119-4","article-title":"The role of the gut microbiota in sepsis","volume":"2","author":"Haak","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.ejphar.2025.178229_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010302","article-title":"Strongyloides stercoralis infection induces gut dysbiosis in chronic kidney disease patients","volume":"16","author":"Hai","year":"2022","journal-title":"PLoS Neglected Trop. Dis."},{"key":"10.1016\/j.ejphar.2025.178229_bib10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejphar.2025.178229_bib11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s40168-023-01659-y","article-title":"The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis","volume":"11","author":"Jin","year":"2023","journal-title":"Microbiome"},{"key":"10.1016\/j.ejphar.2025.178229_bib12","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-023-06378-w","article-title":"Synergy and oxygen adaptation for development of next-generation probiotics","volume":"620","author":"Khan","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2025.178229_bib13","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1038\/s41467-020-15545-w","article-title":"Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejphar.2025.178229_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2021.1875796","article-title":"Blautia-a new functional genus with potential probiotic properties?","volume":"13","author":"Liu","year":"2021","journal-title":"Gut Microbes"},{"key":"10.1016\/j.ejphar.2025.178229_bib15","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1002\/jcsm.13573","article-title":"Short-chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice","volume":"15","author":"Liu","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"10.1016\/j.ejphar.2025.178229_bib16","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00253-015-7039-6","article-title":"Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp.","volume":"100","author":"Liu","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.ejphar.2025.178229_bib17","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1097\/SHK.0000000000002117","article-title":"Global signatures of the microbiome and metabolome during hospitalization of septic patients","volume":"59","author":"Long","year":"2023","journal-title":"Shock"},{"key":"10.1016\/j.ejphar.2025.178229_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2023.106687","article-title":"Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid","volume":"189","author":"Ma","year":"2023","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejphar.2025.178229_bib19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/01.CCM.0000194535.82812.BA","article-title":"The effect of age on the development and outcome of adult sepsis","volume":"34","author":"Martin","year":"2006","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.ejphar.2025.178229_bib20","first-page":"143","article-title":"New insights into the gut as the driver of critical illness and organ failure","volume":"23","author":"Meng","year":"2017","journal-title":"Curr. Opin. Crit. Care"},{"key":"10.1016\/j.ejphar.2025.178229_bib21","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.cell.2024.03.034","article-title":"Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway","volume":"187","author":"Nie","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2025.178229_bib22","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s40168-023-01689-6","article-title":"Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide","volume":"11","author":"Pan","year":"2023","journal-title":"Microbiome"},{"key":"10.1016\/j.ejphar.2025.178229_bib23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13054-024-05232-3","article-title":"A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection among patients admitted to the intensive care unit for sepsis","volume":"29","author":"Park","year":"2025","journal-title":"Crit. Care"},{"key":"10.1016\/j.ejphar.2025.178229_bib24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40168-022-01243-w","article-title":"Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain","volume":"10","author":"Parker","year":"2022","journal-title":"Microbiome"},{"key":"10.1016\/j.ejphar.2025.178229_bib25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of experimental sepsis by cecal ligation and puncture","volume":"4","author":"Rittirsch","year":"2009","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ejphar.2025.178229_bib26","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2025.178229_bib27","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s42003-021-02427-0","article-title":"Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis","volume":"4","author":"Schlatterer","year":"2021","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejphar.2025.178229_bib28","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Shankar-Hari","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.ejphar.2025.178229_bib29","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.ejphar.2025.178229_bib30","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/1040841X.2021.1902940","article-title":"Next-generation probiotics: a promising approach towards designing personalized medicine","volume":"47","author":"Singh","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"10.1016\/j.ejphar.2025.178229_bib31","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13054-023-04412-x","article-title":"Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis","volume":"27","author":"Sun","year":"2023","journal-title":"Crit. Care"},{"key":"10.1016\/j.ejphar.2025.178229_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2024.136578","article-title":"Potential mechanism of CARD16 protein action and susceptibility to sepsis in the elderly infected population: through transcriptome analysis of blood","volume":"281","author":"Sun","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejphar.2025.178229_bib33","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.3390\/nu15061528","article-title":"Role of dietary defatted rice bran in the modulation of gut microbiota in AOM\/DSS-induced colitis-associated colorectal cancer rat model","volume":"15","author":"Tajasuwan","year":"2023","journal-title":"Nutrients"},{"key":"10.1016\/j.ejphar.2025.178229_bib34","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/jama.2020.2717","article-title":"Prevalence and outcomes of infection among patients in intensive care units in 2017","volume":"323","author":"Vincent","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.ejphar.2025.178229_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2022.120333","article-title":"Effect of l-carnitine and mildronate on the mitochondrial metabolism of heart and bacterial composition of the gut microbiome in ageing mice","volume":"293","author":"Volodina","year":"2022","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2025.178229_bib36","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1186\/s13054-023-04777-z","article-title":"Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis","volume":"27","author":"Wang","year":"2023","journal-title":"Crit. Care"},{"key":"10.1016\/j.ejphar.2025.178229_bib37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40168-024-02001-w","article-title":"Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer's disease pathologic process via GPR41 and GPR43","volume":"13","author":"Wang","year":"2025","journal-title":"Microbiome"},{"key":"10.1016\/j.ejphar.2025.178229_bib38","doi-asserted-by":"crossref","first-page":"15747","DOI":"10.1021\/acs.jafc.2c04354","article-title":"Oryzanol ameliorates DSS-stimulated gut barrier damage via targeting the gut microbiota accompanied by the TLR4\/NF-\u03baB\/NLRP3 cascade response in vivo","volume":"70","author":"Xia","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.ejphar.2025.178229_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2025.141711","article-title":"Effects of molecular weight on simulated digestion and fecal fermentation of polysaccharides from longan pulp in vitro","volume":"306","author":"Xia","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejphar.2025.178229_bib40","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1161\/ATVBAHA.121.316883","article-title":"Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing reveals cellular and molecular dynamics of aortic aging in mice","volume":"42","author":"Xie","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.ejphar.2025.178229_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fvets.2022.1076906","article-title":"Effects of Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed on growth performance and gut microbiota of nursery pigs","volume":"9","author":"Yang","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"10.1016\/j.ejphar.2025.178229_bib42","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2022.2154552","article-title":"Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans","volume":"15","author":"Ye","year":"2023","journal-title":"Gut Microbes"},{"key":"10.1016\/j.ejphar.2025.178229_bib43","doi-asserted-by":"crossref","first-page":"22588","DOI":"10.18632\/aging.203572","article-title":"GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis","volume":"13","author":"Zhang","year":"2021","journal-title":"Aging"},{"key":"10.1016\/j.ejphar.2025.178229_bib44","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s42255-022-00715-5","article-title":"TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis","volume":"5","author":"Zhang","year":"2023","journal-title":"Nat. Metab."},{"key":"10.1016\/j.ejphar.2025.178229_bib45","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1136\/annrheumdis-2021-221985","article-title":"Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity","volume":"81","author":"Zhao","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.ejphar.2025.178229_bib46","first-page":"151","article-title":"Akkermansia muciniphila-derived acetate activates the hepatic AMPK\/SIRT1\/PGC-1\u03b1 axis to alleviate ferroptosis in metabolic-associated fatty liver disease","volume":"13","author":"Zhuge","year":"2024","journal-title":"Acta Pharm. Sin. B"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925009835?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925009835?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:28:36Z","timestamp":1779323316000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925009835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":46,"alternative-id":["S0014299925009835"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178229","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2\/NLRP3 pathway","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178229","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"178229"}}