{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:45:08Z","timestamp":1792611908308,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging is associated with profound alterations in gut microbiota composition and function, including reduced production of short\u2010chain fatty acids (SCFAs), yet it remains unclear whether these age\u2010related microbial changes directly contribute to impaired antiviral defense during influenza A virus (IAV) infection. To address this question, we first characterized age\u2010associated alterations of the gut microbiome and SCFA\u2010related metabolic potential in a murine model of IAV infection. We then used a complementary human senescent lung fibroblast model to determine whether acetate, a major microbiota\u2010derived SCFA, directly modulates antiviral responses in aging\u2010associated lung cells. In old mice, IAV infection was associated with marked microbiota dysbiosis, including reduced abundance of SCFA\u2010producing commensals such as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:italic>Faecalibaculum rodentium<\/jats:italic>\n                    , accompanied by decreased expression of microbial pathways involved in carbohydrate fermentation and acetate production. These findings suggested impaired microbiota\u2010derived metabolic support of antiviral immunity during aging. Based on these observations, mechanistic studies in senescent human lung fibroblasts demonstrated that acetate supplementation significantly reduced viral replication and inflammatory responses. These protective effects were associated with FFAR2\/FFAR3 signaling and enhanced histone H3 acetylation, indicating metabolic and epigenetic modulation of the antiviral response. Together, our findings establish a translational link between aging\u2010associated gut microbiota dysfunction and impaired antiviral defense by combining a murine model of aging and influenza infection with mechanistic validation in human senescent lung cells. They identify acetate as a potential mediator of the gut\u2013lung axis and support microbiota\u2010targeted interventions to reduce influenza severity in older individuals.\n                  <\/jats:p>","DOI":"10.1111\/acel.70750","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:09:25Z","timestamp":1791364165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010Associated Gut Microbiota Dysbiosis Impairs Antiviral Defense During Influenza Virus Infection and Identifies Acetate as a Protective Mediator in Senescent Human Lung Cells"],"prefix":"10.1111","volume":"25","author":[{"given":"Christoph","family":"Wernike","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology Jena University Hospital  Jena Germany"},{"name":"Else Kr\u00f6ner Graduate School for Medical Students \u201cJSAM\u201d Jena University Hospital  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-1754","authenticated-orcid":false,"given":"Antje","family":"H\u00e4der","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology Jena University Hospital  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9757-5036","authenticated-orcid":false,"given":"Yasmina","family":"Reisser","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology Jena University Hospital  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-4666","authenticated-orcid":false,"given":"Kiana","family":"Garakani","sequence":"additional","affiliation":[{"name":"Medicine\/Pulmonary and Critical Care Division University of California San Francisco  San Francisco California 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