Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites:A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum) CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62) were randomly assigned to receive placebo(N=31) or B.longum CCFM1077(1 × 1010colony-forming units(CFUs) per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C) were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA) sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p <0.01) and LDL-C(p <0.01) in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine) and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms) were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.