{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:30:00Z","timestamp":1793046600992,"version":"4.5.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>Sepsis frequently involves early gastrointestinal dysfunction, in which intestinal barrier breakdown and microbiota dysbiosis amplify systemic inflammation and contribute to multi-organ failure. Emerging evidence indicates that the gut is not merely a bystander in sepsis but an active driver of pathogenic cascades through epithelial injury, mucosal immune dysregulation, ischemia\u2013reperfusion stress, and impaired motility, collectively promoting microbial translocation and immune deviation. In parallel, sepsis is associated with profound remodeling of the gut microbiome, characterized by reduced commensal diversity, expansion of pathobionts, and functional shifts in key microbial metabolites, including short-chain fatty acids, bile acids, and tryptophan-derived products, which further compromise mucosal integrity and host immune tone. This narrative review synthesizes experimental, translational, and clinical findings to elucidate the bidirectional interaction gut barrier\u2013microbiota interplay in sepsis and to summarize mechanistic links across epithelial, immune, and metabolic signaling pathways, including gut-liver and gut-brain axes relevant to sepsis-associated organ dysfunction. dysfunctional microbial community leads to systemic immune deviation, multi-organ dysfunction and sepsis-associated encephalopathy, a common and severe neurological complication of sepsis. We also discuss emerging therapeutic strategies targeting the gut\u2013microbiota axis\u2014such as early enteral nutrition, prebiotics\/postbiotics, defined microbial consortia, fecal microbiota transplantation, and metabolite-based supplementation\u2014and evaluate their potential and limitations in septic populations. Finally, we highlight key challenges, including unresolved causality, inter-individual variability, context-dependent responses, and safety concerns, underscoring the need for longitudinal multi-omic profiling, host\u2013microbiome phenotyping, and mechanism-informed interventional trials to enable precision microbiome-based approaches for sepsis.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1761536","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:25:27Z","timestamp":1776317127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The interplay between gastrointestinal dysfunction and gut microbiota dynamics in sepsis"],"prefix":"10.3389","volume":"16","author":[{"given":"Lirong","family":"Zheng","sequence":"first","affiliation":[{"name":"Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Jia","sequence":"additional","affiliation":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Su","sequence":"additional","affiliation":[{"name":"Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","first-page":"363","article-title":"Epithelial layer dysfunction in inflammatory bowel diseases: the role of tight junction proteins","author":"Acat","year":"","journal-title":"Broad. 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