Multi level effects of Sanghuang Tongxie Formula on type 2 diabetes rats: a comprehensive analysis from intestinal bacteria to metabolome and transcriptome.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive β-cell dysfunction and peripheral insulin resistance, leading to dysregulated glucose homeostasis and sustained low-grade inflammation. This study aimed to evaluate the therapeutic efficacy of the traditional Chinese medicine, Sanghuang Tongxie Formula (SHTX), in a rat model of T2DM and to elucidate its underlying mechanisms by analyzing gut microbiota composition, metabolic pathways, and gene expression profiles using metabolomics and transcriptomics. METHODS: A Type 2 diabetes mellitus model was established in Sprague-Dawley (SD) rats through a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). The therapeutic effects of SHTX on the gut microbiota, metabolic pathways, and gene expression were evaluated through high-throughput sequencing and comprehensive metabolomics analysis. RESULTS: SHTX treatment significantly altered the gut microbiota composition in T2DM rats, increasing the relative abundance of Bacteroidetes while decreasing that of Firmicutes, which was closely correlated with improved insulin sensitivity. Metabolomics analysis revealed that SHTX modulated the glycerophospholipid metabolic pathway, resulting in significant alterations in key metabolites. Notably, genes involved in glycerophospholipid metabolism, such as Plin2 and PLD1, showed marked changes in expression in response to SHTX treatment. Additionally, transcriptomic profiling demonstrated that SHTX profoundly impacted multiple metabolic and regulatory pathways in the liver, with a particular focus on those associated with glycerophospholipid metabolism. CONCLUSION: These results suggest that SHTX treatment may improve metabolic homeostasis in T2DM by modulating gut microbiota and several key metabolic pathways, particularly glycerophospholipid metabolism. However, the study has several limitations, including the reliance on animal models and the incomplete elucidation of the underlying mechanisms. Further studies are needed to confirm these findings and explore the molecular mechanisms of SHTX therapy. Additionally, clinical trials are necessary to assess the therapeutic potential and efficacy of SHTX in human T2DM patients.