{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:16:46Z","timestamp":1793229406265,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The interplay between sedative agents and the gut microbiome may influence long-term outcomes in sepsis, but data are scarce. This study compared the effects of dexmedetomidine vs. propofol sedation on long-term survival in mechanically ventilated sepsis adults, with an exploratory focus on the gut microbiome and pre-existing malignancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicenter, retrospective cohort study, 1,295 mechanically ventilated adults with sepsis (2013\u20132020) were analyzed. Propensity score matching (1:1) balanced 27 baseline covariates, producing 177 matched pairs. Primary outcomes were 30-day, 90-day, and 5-year mortality. Secondary outcomes included delirium\/coma-free days, cardiovascular safety, and 6-month functional status. Subgroup analyses assessed pre-existing malignancies and high antibiotic exposure (\u22657 days before enrollment) as proxies for microbiome disruption. Gut microbiota composition was characterized via 16S rRNA sequencing in a pre-specified subcohort (\n                      <jats:italic>n<\/jats:italic>\n                      = 89).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After matching, dexmedetomidine was associated with significantly lower 5-year mortality (34.5% vs. 45.2%; HR 0.64, 95% CI 0.52\u20130.79;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.039). Survival curves progressively diverged beyond 180 days. No differences were observed in short-term neurological outcomes or cardiovascular safety. Subgroup analyses showed enhanced survival benefits with dexmedetomidine in patients aged &amp;gt;65, females, those with pulmonary-source sepsis, SOFA &amp;gt;10, baseline delirium, pre-existing malignancies (OR 2.10, 95% CI 1.15\u20133.85;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.015), and high antibiotic exposure as a proxy for gut dysbiosis (OR 1.95, 95% CI 1.08\u20133.52;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.028). Exploratory 16S rRNA analysis in a subset (\n                      <jats:italic>n<\/jats:italic>\n                      = 89) revealed that dexmedetomidine was associated with enriched beneficial genera such as\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      and\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      , while propofol correlated with increased\n                      <jats:italic>Enterococcus<\/jats:italic>\n                      and\n                      <jats:italic>Escherichia\/Shigella<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dexmedetomidine sedation is associated with a significant 5-year survival benefit in mechanically ventilated sepsis patients, particularly among those with malignancies or factors predisposing to gut dysbiosis. The observed modulation of the gut microbiome toward a more symbiotic state provides a plausible mechanistic insight into these clinical findings, highlighting a potential role for microbiota-centric strategies in critical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1720867","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:33:35Z","timestamp":1764138815000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dexmedetomidine modulates gut microbiota and improves long-term survival in sepsis patients with pre-existing malignancies: a propensity-matched analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yisen","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaijian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1097\/CCM.0b013e3181c03dfa","article-title":"Cardioprotection, attenuated systemic inflammation, and survival benefit of \u03b21-adrenoceptor blockade in severe sepsis in rats","volume":"38","author":"Ackland","year":"2010","journal-title":"Crit. 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