Supplemented Xijiao Dihuang Decoction alleviates sepsis via modulation of gut microbiota and metabolites: A multi-omics approach

Sepsis, a critical condition that is a leading cause of mortality in critically ill patients, involves complex interactions between host genetics and environmental factors. The present study evaluated the therapeutic efficacy and mechanisms of action of supplemented Xijiao Dihuang Decoction (SXJDHD), a traditional Chinese medicine (TCM) formula augmented with additional herbs, in treating sepsis. Using a multi-omics approach encompassing metabolomics and gut microbiota analysis, we investigated the effects of SXJDHD on sepsis outcomes. Network pharmacology analysis revealed that SXJDHD targets multiple pathways implicated in sepsis pathogenesis. In a mouse model of sepsis, SXJDHD significantly improved survival rates, alleviated multi-organ damage, and reduced the levels of inflammatory cytokines TNF- α and IL-6. Additionally, SXJDHD modulated the gut microbiota, increasing the abundance of beneficial bacteria such as Bacteroides and Prevotellaceae UCG-001, while decreasing that of Helicobacter. Metabolomics analysis showed significant changes in microbial metabolites following SXJDHD intervention, suggesting modulation of the metabolome. Collectively, these findings indicate that SXJDHD exhibits therapeutic potential in sepsis through the regulation of gut microbiota and metabolites, providing insights into the mechanisms underlying its efficacy. The study evaluated Supplemented Xijiao Dihuang Decoction (SXJDHD), a traditional Chinese medicine, for treating sepsis. Using multi-omics and network pharmacology, it was found that SXJDHD targets multiple sepsis pathways. In a mouse model, SXJDHD improved survival, reduced organ damage, and lowered inflammatory cytokines. It also modulated the gut microbiota, increasing beneficial bacteria and altering microbial metabolites. These findings suggest SXJDHD's therapeutic potential in sepsis through gut microbiota and metabolite regulation.