EC Microbiology

Background: Liver fibrosis affects approximately 844 million people globally, representing a significant public health challenge. The gut-liver axis and its associated bacterial metabolites have emerged as crucial mediators in liver pathophysiology, offering new perspectives on disease progression and potential therapeutic interventions.

Purpose: This review aims to comprehensively analyze the role of bacterial metabolites in liver fibrosis, examining their mechanistic pathways, diagnostic potential, and therapeutic applications through advanced metabolomic approaches.

Methods and Findings: Recent advances in mass spectrometry and NMR spectroscopy have revealed complex interactions between bacterial metabolites and liver fibrosis progression. Key metabolites, including lipopolysaccharides (LPS), secondary bile acids, and short-chain fatty acids (SCFAs), demonstrate distinct mechanistic roles through specific pathways. LPS influences fibrogenesis via TLR4-mediated signaling and non-canonical inflammasome activation. Secondary bile acids modulate FXR and TGR5 signaling pathways, while SCFAs exhibit significant anti-inflammatory properties through GPR41/43 receptor activation and epigenetic modifications. Dysbiosis in liver disease manifests through reduced bacterial diversity, particularly affecting Lachnospiraceae and Ruminococcaceae families, with concurrent increases in Enterobacteriaceae. Integration of multi-omics approaches has identified novel metabolite signatures associated with disease progression, enabling the development of more accurate diagnostic biomarkers and personalized therapeutic strategies.

Conclusion: Understanding bacterial metabolites' role in liver fibrosis has revolutionized our approach to disease management, offering promising avenues for early detection and targeted therapy. While technical challenges and biological complexity persist, ongoing advances in metabolomic technologies and analytical approaches continue to enhance our ability to develop effective diagnostic and therapeutic strategies for liver fibrosis.

 Keywords: Gut-Liver Axis Dysbiosis; Bacterial Metabolomics; Liver Fibrogenesis; Metabolite-Based Therapeutics; Multi-Omics Integration

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