ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
This article is part of the Research TopicMicrobiome and its Roles in Disease Diagnosis and Treatment: Pathogen Resistance Spectrum, Metabolism, Risk Model, and Vaccine DesignView all 6 articles
Dexmedetomidine Modulates Gut Microbiota and Improves Long-Term Survival in Sepsis Patients with Pre-existing Malignancies: A Propensity-Matched Analysis
Provisionally accepted
- 1Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Zhangzhou, China
- 2The First Affiliated Hospital of Xiamen University, Xiamen, China
- 3Fujian Medical University Union Hospital, Fuzhou, China
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Abstract Background: 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 versus propofol sedation on long-term survival in mechanically ventilated sepsis adults, with an exploratory focus on the gut microbiome and pre-existing malignancies. Methods: In this multicenter, retrospective cohort study, 1,295 mechanically ventilated adults with sepsis (2013–2020) 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 (≥7 days before enrollment) as proxies for microbiome disruption. Gut microbiota composition was characterized via 16S rRNA sequencing in a pre-specified subcohort (n=89). Results: After matching, dexmedetomidine was associated with significantly lower 5-year mortality (34.5% vs. 45.2%; HR 0.64, 95% CI 0.52–0.79; p=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 >65, females, those with pulmonary-source sepsis, SOFA >10, baseline delirium, pre-existing malignancies (OR 2.10, 95% CI 1.15–3.85; p=0.015), and high antibiotic exposure as a proxy for gut dysbiosis (OR 1.95, 95% CI 1.08–3.52; p=0.028). Exploratory 16S rRNA analysis in a subset (n=89) revealed that dexmedetomidine was associated with enriched beneficial genera such as Faecalibacterium and Bifidobacterium, while propofol correlated with increased Enterococcusand Escherichia/Shigella. Conclusions: 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 towards a more symbiotic state provides a plausible mechanistic insight into these clinical findings, highlighting a potential role for microbiota-centric strategies in critical care.
Keywords: tumor, Sepsis, gut microbial colonization, Dexmedetomidine, host-microbiota interaction mechanisms, clinical microbiota interventions, tumor-microbiota axis, Microbiota-based therapy
Received: 08 Oct 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Zeng, Wu, Zhang, Ye, Chen and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yibin Ye, yybeiin@163.com
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