Amorphophallus konjac via Gut Microbiota‐FXR/FGF15 Axis Changed Bile Acid Metabolism in Hyperlipidemia Mice

Background: Hyperlipidemia (HLP) is highly prevalent in China, and this prevalence is increasing annually, particularly among younger populations. The extract of Amorphophallus konjac (APK), a traditional food and medicinal plant in China, has shown potential hypoglycemic and antitumor effects. However, the therapeutic efficacy and underlying mechanisms of its water extract (APKW) in HLP remain unclear. Method: An HLP model was established in mice by feeding them a high‐fat diet. The mice were then treated with APKW (12 g/kg and 6 g/kg) for 14 weeks. Efficacy was assessed through measurements of body weight, serum and hepatic lipid profiles, and histopathological examination. Gut microbiota composition was analyzed using 16S rRNA sequencing, while bile acid (BA) levels in serum and feces were determined through UPLC‐MS. Finally, the expression of genes and proteins involved in the FXR/FGF15 and GATA4/ASBT signaling pathways in the ileum or liver was analyzed through qPCR and western blotting. Results: APKW treatment significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low‐density lipoprotein cholesterol. Hepatic levels of TC and TG were also lowered, accompanied by improved liver histopathology. Moreover, 16S rRNA sequencing unveiled that APKW increased the abundance of g_Lactobacillus and g_Ileibacterium while reducing the abundance of g_Monoglobuss . Bile acid profiling showed reduced serum levels of cholic acid (CA), chenodeoxycholic acid (CDCA), lithocholic acid, and ursodeoxycholic acid, as well as declined fecal levels of CA, CDCA, taurocholic acid, taurochenodeoxycholic acid, glycoursodeoxycholic acid, and deoxycholic acid. The western blotting, PCR, and immunofluorescence results revealed that APKW inhibited the intestinal FXR‐FGF15 signaling pathway and ASBT expression while upregulating hepatic expression of CYP7A1, FGFR4, and FXR. This suggests enhanced hepatic BA synthesis, reduced ileal BA reabsorption, decreased hepatic cholesterol levels, and suppressed lipogenesis. Conclusion: This study is the first to demonstrate that APKW ameliorates HLP by remodeling gut microbiota, regulating BA metabolism, and modulating the FXR/FGF15 and GATA4/ASBT signaling pathways.