Mechanisms of Gui Zhi Fu Ling Formula in Liver Fibrosis: Metabolomics and Gut Microbiota Analysis

ABSTRACT The Gui Zhi Fu Ling Formula (GZFLF), a classical traditional Chinese medicine prescription originating from the Shanghan Lun , is traditionally used to promote blood circulation and alleviate blood stasis. Modern medical research has demonstrated its anti‐inflammatory and anti‐fibrotic effects. This study aimed to identify the therapeutic effect, potential targets and mechanisms of GZFLF in hepatic fibrosis through metabolomics and gut microbiota analysis. By combining these results with literature research, we focused on the metabolite eicosapentaenoic acid (EPA) as a beneficial marker metabolite. Furthermore, marker microbial taxa, including Pseudomonas , were identified from the gut microbiota analysis, which may be relevant to the GZFLF intervention. Finally, we examined the interrelationships among gut microbiota, metabolomics, and serological analyses. This study shows that GZFLF may ameliorate liver fibrosis potentially associated with increased hepatic EPA and gut Pseudomonas abundance. We further speculate a potential correlation between these factors. Further studies will be conducted to validate this hypothesis and elucidate the underlying mechanisms.