Gut microbiota mediates the anti-obesity effects of Gnaphalium affine methanol extract in HFD-induced obesity

Background Obesity constitutes a pressing global public health challenge, characterized by intricate associations with metabolic dysregulation and gut microbiota dysbiosis. Methods This study systematically evaluated the anti-obesity efficacy and underlying mechanisms of Gnaphalium affine methanol extract (GAE) in high-fat diet (HFD)-induced obese mice, with integrated fecal microbiota transplantation (FMT) experiments to establish causal relationships between GAE-modulated gut microbiota and metabolic improvements. Results GAE intervention significantly ameliorated HFD-induced metabolic disorders, as evidenced by reduced oxidative stress, enhanced glucose tolerance, suppressed visceral adiposity, and attenuated chronic low-grade inflammation. Mechanistically, GAE preserved intestinal barrier integrity through upregulation of tight junction protein expression. Multi-omics integration of 16S rRNA gene sequencing and untargeted metabolomics revealed that GAE substantially rectified gut microbiota dysbiosis and lipid metabolic disturbances, mediated by specific bioactive metabolites—including lysophosphatidylcholine 22:6 and N-oleoyl glycine—and enrichment of beneficial bacterial genera ( Phascolarctobacterium and Lactobacillus ). Critically, FMT experiments demonstrated that the gut microbiota remodeled by GAE administration was sufficient to transfer obesity-alleviating phenotypes to recipient mice. Conclusion Collectively, these findings establish that GAE exerts multi-target anti-obesity effects through modulation of the “microbiota–gut–metabolism” axis, providing compelling preclinical evidence supporting the development of GAE as a functional food ingredient for weight management applications.