Synbiotic AHY improves hyperlipidemia in high-fat diet-fed mice by activating the gut-liver axis through modulation of the gut microbiota

In our previous study, a synbiotic AHY improved constipation was developed using 3 probiotic strains Lactiplantibacillus plantarum Y12, AHQ-14 and HM22) and four prebiotics (stachyose, fructooligosaccharides, isomaltooligosaccharide and galactooligosaccharides). The in vitro cholesterol-scavenging capacity of 3 probiotic strains was assessed, revealing that AHY may possess lipid-lowering potential. Consequently, the in vivo lipid-lowering efficacy of AHY was evaluated by establishing a hyperlipidemia model using high-fat diet (HFD)-fed C57BL/6J mice and administering AHY over a period of 12 weeks. Various parameters including biochemical indexes, histological morphology, metabolites, gene expression and intestinal flora were analyzed to evaluate the hypolipidemic effect of AHY in vivo. The results demonstrated that gavage administration of AHY led to a significant reduction in body weight and organ indexes, as well as an improvement in lipid abnormalities in serum. Moreover, AHY significantly reduced serum total bile acids (TBAs) and significantly increased fecal TBAs. Furthermore, AHY up-regulated tight junction proteins (claudin-1, ZO-1, occludin) and down-regulated inflammatory factors (interleukin-6, interleukin-1β, tumor necrosis factor-α), enhancing intestinal barrier function and reducing colon inflammation. Additionally, AHY influenced the composition of gut microbiota by increasing beneficial bacteria (Lactobacillus, Bifidobacterium) and decreasing harmful bacteria (norank_f_Desulfovibrionaceae, norank_f_Oscillospiraceae), resulting in higher level of short-chain fatty acids (SCFAs) in the gut. This modulation of bacterial flora contributed to the regulation of cholesterol metabolism through activating the gut-liver axis pathway, effectively reducing blood lipid levels. These findings suggest that AHY have the potential to be a functional synbiotic for alleviating hyperlipidemia and offers novel insights to understand the mechanism for probiotic products alleviating hyperlipidemia.