Dietary aqueous extract of Astragalus sinicus alleviates obesity by reshaping gut microbiota and metabolism

BACKGROUND: Obesity induced by long-term high-fat diet (HFD) consumption is closely associated with metabolic disorders and gut microbiota dysbiosis. Although plant-derived extracts show anti-obesity potential, microbiota-dependent mechanisms and causal relevance remain incompletely understood. Astragalus sinicus L. is a traditional medicinal and dietary plant, yet the metabolic effects of its aqueous extract have not been systematically evaluated. This study investigated the anti-obesity effects of an aqueous extract of Astragalus sinicus (ASAE) and determined whether gut microbiota remodeling mediates its metabolic benefits. HFD-induced obese mice were treated with ASAE and subjected to comprehensive metabolic phenotyping. The chemical composition of ASAE was characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Gut microbiota composition, fecal metabolomic profiles, and adipose tissue transcriptomes were analyzed using 16S rRNA gene sequencing, untargeted metabolomics, and RNA sequencing, respectively. Fecal microbiota transplantation was performed to assess microbiota-dependent causality. RESULTS: ASAE significantly improved glucose tolerance, insulin sensitivity, dyslipidemia, and hepatic steatosis in HFD-fed mice without affecting food intake. ASAE markedly reshaped gut microbiota structure and fecal metabolomic profiles, particularly regulating steroid- and lipid-related metabolites. Adipose transcriptomic analysis revealed that ASAE reversed HFD-induced transcriptional programs associated with immune activation and lipid metabolic dysfunction. Importantly, transplantation of microbiota from ASAE-treated donors recapitulated these metabolic improvements in obese recipient mice, demonstrating a microbiota-dependent effect. CONCLUSION: ASAE alleviates HFD-induced obesity through gut microbiota-mediated mechanisms, providing causal evidence linking microbial remodeling to host metabolic improvement. These findings highlight ASAE as a promising microbiota-targeted intervention for obesity. © 2026 Society of Chemical Industry.