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.