REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
This article is part of the Research TopicGut microbiome-driven Pathogenesis and Intervention Strategies in Liver DiseasesView all 7 articles
Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications
Provisionally accepted
- Bengbu Medical University, Bengbu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Cirrhosis remains a significant global health burden, causing approximately 1.4–1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut–liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30–60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)–producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40–70%, accompanied by a two-to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions—including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators—restore community balance in 70–85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome–metabolome models achieve areas under the curve (AUCs) of 0.82–0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome–metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.
Keywords: cirrhosis, gut liver axis, Intestinal dysbiosis, bile acid signaling, fecal microbiotatransplantation
Received: 02 Oct 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Chang, Liu, Yan, Li, Wu, Chen, Ma, Zhao, Chen and Zhang. 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: Jing Zhang, alvarezanthony7432@outlook.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.