The Prebiotic Effect of Kaempferol in Regulating Bile Acid Metabolism

ABSTRACT Kaempferol (Kae), as a homologous flavonoid, plays a pivotal role in human nutrition and disease treatment. This study endeavors to elucidate the in vivo metabolism of Kae and its potential to modulate the interplay between bile acids (BAs) and gut microbiota (GM). After Kae administration, we analyzed pharmacokinetics, BA levels, and drug metabolic enzymes (DMEs) amount using LC–MS/MS. Subsequently, we checked the gene and protein expression with qRT‐PCR and western blot and studied the changes in GM using 16S rRNA sequencing, accompanying in‐depth data analysis. Finally, molecular docking was employed to explore Kae's interaction with the Farnesoid X receptor (FXR). Kae enhances its own absorption and metabolic circulation in vivo by upregulating the UDP‐Glucuronosyltransferases (UGTs) expression. Furthermore, Kae significantly suppressed the expression of cholesterol 7α‐hydroxylase (CYP7A1) while concurrently elevating the sterol 27‐hydroxylase (CYP27A1) expression, by activating the liver FXR, a nuclear transcription factor involved in the regulation of CYPs and UGTs enzymes. For BA analysis, Kae induced the upregulation of tauro‐BAs by attenuating the activity of bile salt hydrolases (BSH), which correlated with shifts in the GM composition. Specifically, Kae increased the abundance of beneficial bacteria such as Bacteroides acidifaciens and Bifidobacterium choerinum , while reduced populations of species associated with BSH deconjugation. The study indicates that Kae may serve as a prebiotic, modulating the BA‐GM interaction to confer nutritional and therapeutic advantages.