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Recent evidence positions gut microbiota dysbiosis and nitric oxide (NO) dysregulation as central, interacting pathophysiological mechanisms in cirrhosis progression. Intestinal barrier dysfunction facilitates bacterial translocation and thereby exposes the liver to lipopolysaccharides and pathogen-associated molecular patterns that trigger hepatic inflammation via Toll-like receptor signalling, a phenomenon aggravated by dysbiosis. This immune activation stimulates inducible NO synthase in Kupffer cells and systemic endothelium, generating excess NO that drives splanchnic vasodilation and worsens portal hypertension. Paradoxically, intrahepatic endothelial NO synthase activity becomes impaired, reducing sinusoidal NO availability and increasing intrahepatic vascular resistance. These interconnected disturbances perpetuate inflammation and fibrogenesis, contributing to cirrhosis decompensation and spontaneous bacterial peritonitis. Despite substantial mechanistic insight into these pathways, therapeutic translation remains limited. Statins show promise by restoring intrahepatic eNOS function and reducing portal pressure, while microbiota-targeted interventions (antibiotics, probiotics, fecal transplantation) address gut-derived inflammation. This review synthesizes our current understanding of the gut-liver-NO axis in cirrhosis, highlighting how dysbiosis and aberrant NO signalling reinforce each other through inflammatory feedback loops, and identifies critical gaps between mechanistic knowledge and clinical application that warrant further investigation.<\/jats:p>","DOI":"10.1007\/s13105-026-01188-w","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:26:22Z","timestamp":1778153182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut dysbiosis and nitric oxide dysregulation in cirrhosis progression: mechanistic insights and pathophysiological implications"],"prefix":"10.1007","volume":"82","author":[{"given":"Vlad","family":"R\u0103zniceanu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andra","family":"\u021aichindeleanu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugen-Valentin","family":"R\u0103ducu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0218erban Ellias","family":"Trella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iuliana","family":"Nenu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"issue":"23","key":"1188_CR1","doi-asserted-by":"publisher","first-page":"7312","DOI":"10.3748\/wjg.v20.i23.7312","volume":"20","author":"WC Zhou","year":"2014","unstructured":"Zhou WC (2014) Pathogenesis of liver cirrhosis. 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