Electroacupuncture-induced gut microbiota alterations correlate with FXR/FGF15 activation and metabolic improvement in hyperlipidemic rats

This study aimed to explore the association between the effect of electroacupuncture (EA) in improving hyperlipidemia and changes in the intestinal flora and bile acid metabolism, and to preliminarily investigate its possible molecular basis. Wistar rats were stratified into five groups: control, model, sham EA, EA, and EA+FXR agonist. Comprehensive assessments included hepatic histopathology (H&E staining), serum lipid profiling (TC, TG, LDL-C, HDL-C), 16S rDNA sequencing of gut microbiota, targeted bile acid metabolomics, and molecular analyses (Western blot, immunohistochemistry and qRT-PCR) of FXR/FGF15 pathway components and associated enzymes (CYP7B1, CYP27A1). EA intervention significantly attenuated hyperlipidemia manifestations by reducing body weight, improving hepatic steatosis, and normalizing serum lipid parameters. Gut microbiota analysis revealed EA-enhanced microbial diversity with specific modulations: decreased Firmicutes / Bacteroidota ratio, enriched Akkermansia and Bacteroidota , and reduced Muribaculum abundance. Targeted metabolomics identified EA-mediated restoration of bile acid metabolism, particularly elevation of secondary bile acids. Molecular analyses demonstrated EA activation of the FXR/FGF15 axis with downstream regulation of hepatic CYP7B1 and CYP27A1. The effect of EA in improving hyperlipidemia is significantly associated with the changes in the structure of the intestinal microbiota and the activation of the FXR/FGF15 signaling pathway. This finding suggests that the metabolic benefits of EA may involve the molecular connection of the gut microbiota-bile acid axis.