Metabolic Mechanisms of Modified Lingguizhugan Decoction in Obesity and Lipid Metabolism Disorders: A Multi‐Omics Approach

Background Obesity and related metabolic disorders, including metabolic dysfunction‐associated fatty liver disease, dyslipidemia, and type 2 diabetes, are pressing global health concerns. Traditional Chinese medicine, specifically modified Lingguizhugan decoction (MLGZGD), has shown promise for managing these conditions. MLGZGD contains bioactive compounds that may modulate lipid metabolism and gut microbiota, suggesting potential therapeutic benefits for obesity and associated metabolic disorders. However, the underlying mechanisms remain largely unknown. This study investigated the therapeutic effects of MLGZGD on obesity and lipid metabolism. Specifically, we sought to examine how MLGZGD influences gut microbiota, modulates lipid metabolism, and contributes to improved metabolic health using a multi‐omics approach. Methods This study identified the active compounds in MLGZGD using UPLC‐Q‐TOF‐MS/MS. The mice were divided into four groups ( n = 8 per group) and received different treatments: model, positive control (atorvastatin 2.6 mg kg −1 ), low‐dose MLGZGD (7 g kg −1 ), or high‐dose MLGZGD (14 g kg −1 ). The effects of MLGZGD on the gut microbiota and lipid metabolism were evaluated using 16S rRNA sequencing and lipidomic analysis, and correlations between the two were explored. Results In normal mice, MLGZGD significantly altered the gut microbiota composition, increasing the abundance of beneficial genera such as Akkermansia and Dubosiella , while reducing the abundance of Enterorhabdus . In high‐fat diet‐induced obese mice, MLGZGD restored the disrupted gut microbiota, notably reducing the Firmicutes/Bacteroidetes ratio, improving Akkermansia levels, and increasing Clostridiales abundance. Lipidomic analysis showed that MLGZGD significantly improved triglyceride and phosphatidylcholine metabolism, with a notable correlation between Akkermansia and Clostridiales abundance and the lipid profile. Conclusions MLGZGD effectively ameliorates obesity and lipid metabolism‐related disorders by reshaping the gut microbiota and modulating lipid metabolism. These findings support the therapeutic potential of MLGZGD in treating obesity and related metabolic disorders, with modulation of gut microbiota and lipid metabolism as key mechanisms.