Microorganisms and Organ Fibrosis: Research Advances from Mechanisms to Therapeutics

Organ fibrosis is a common pathological endpoint of chronic diseases. It is characterized by excessive deposition of extracellular matrix (ECM) and gradual destruction of tissue structure, which eventually leads to organ failure. There is still a lack of effective reversal strategies. Recent advances in macrogenomics have revealed the key regulatory role of microbiomes in fibrosis, extending this paradigm beyond chronic inflammation. This review integrates the current progress. First, it explores the relationship between local microbiome (intestine, lung, skin, reproductive tract) and local fibrosis, and then studies how intestinal and oral microbiomes pass through the interorgan axis (intestinal-liver, intestinal-lung, intestinal-kidney, intestinal-skin, oral-liver, mouth Cavity-lung, mouth-kidney) mediates distal organ fibrosis. Four common mechanisms are summarized: transformation growth factor-β (TGF-β) signal transduction, microbial-related molecular pattern (MAMPs)-Toll-like receptor (TLRs) signal transduction, metabolite-mediated effects, and epithelial barrier destruction. In addition, the diagnostic efficacy of biomarkers and microecological interventions based on microbiome, including probiotics/prebiotics, fecal microbioma transplantation and engineered probiotics, were reviewed. It discusses challenges including technical limitations and causality establishment, as well as future research directions, such as spatial macrogenomics, AI-driven multi-omics integration and new target development. Overall, this work provides a framework for the development of anti-fibrosis strategies for microbiome.