Fenofibrate positively affects gene expression profiles and metabolic pathway of high-fat diet-treated hamsters gut microbiota

Abstract

Background: Fenofibrate is a compound with diverse biological properties that can be utilized to lower blood lipids. Understanding the impact of the gut microbiota in hyperlipidemia is vital for controlling systemic inflammation and improving serum lipid control. Nevertheless, the specific effects of fenofibrate on the phenotype and gene expression of resident gut bacteria, as well as its influence on the transformation of microbial metabolism into functional networks, remain unclear. In this study, our aimed to examine the gene expression profile and metabolic pathways of the gut microbiota in a hamster model fed a high-fat diet (HFD) and administered fenofibrate. Results: The results indicated that the group treated with fenofibrate exhibited higher levels of beneficial bacterial species associated with health, including Bacteroides ovatus, Bifidobacterium animalis, Bacteroides intestinalis, Allobaculum stercoricanis, Lactobacillus reuteri, and Bacteroides acidifaciens, in comparison to the HFD group. Additionally, analysis of metabolic pathways demonstrated that dietary fenofibrate significantly enhanced the biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and pyrimidine metabolism, while reducing glyoxylate and dicarboxylate metabolism, tyrosine metabolism, tryptophan metabolism, and nonribosomal peptide structures. Furthermore, these metabolic pathway changes were associated with relative alterations in the abundance of genes from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, namely K01667, K11358, K13953, K04072, K06131, K00655, K04567, K02864, K06409, K05366, K01867, K21071, and K13292. Moreover, significant changes were observed in the expression of enzymes and genes related to carbohydrate and antibiotic resistance, such as glycosyltransferase family 51 (GT51) as well as adeC, carA, and MexT. Conclusions: Dietary fenofibrate exerted significant effects on genes and pathways related to lipid, energy, and amino acid metabolism, ultimately promoting a healthier colonic environment for the host. And these findings contribute to a better understanding of the mechanism of action of fenofibrate and provide a valuable foundation for future experimental and clinical studies, aiming to explore its practical applications.