Lactobacillus fermentum 166, Derived from Yak Yogurt from Tibetan Areas of Sichuan, Improves High-Fat-Diet-Induced Hyperlipidemia by Modulating Gut Microbiota and Liver- and Gut-Related Pathways

The consumption of an unbalanced diet, such as a high-fat diet, is strongly associated with hyperlipidemia and significantly contributes to the development of cardiovascular and cerebrovascular diseases, which are the leading causes of death worldwide. Globally, about 17.9 million people die of cardiovascular disease each year (WHO 2023). Probiotics have emerged as a promising intervention to alleviate hyperlipidemia. Therefore, this study investigates the effects of Lactobacillus fermentum 166 (LF-166), isolated from yak yogurt in the Sichuan Tibetan area, on lipid metabolism in the liver and gut microbiota of high-fat-diet-induced hyperlipidemic mice. The results revealed that the Lactobacillus fermentum 166 (LF-166) treatment reduced the body weight and decreased the blood and liver lipid levels in these mice. Based on the histopathological findings, LF-166 could alleviate liver steatosis and colon injury. Additionally, 16S rRNA sequencing of the mice's colonic contents showed that LF-166 reduced the Firmicutes/Bacteroidetes (F/B) value and enhanced the richness and diversity of the gut microbiota. LF-166 regulated hepatic lipid metabolism through the up-regulation of the genes Lxr, Ampkα, Fxr, Hsl, and Atgl and the down-regulation of C/ebpα and Pparγ in the liver; it also regulated intestinal lipid metabolism by up-regulating Abcg5 and Abcg8 in the ileum and down-regulating the expression of the genes Npc1l1, Asbt, and Ibabp. Thus, LF-166 may inhibit hyperlipidemia progression by modulating the expression of key genes involved in hepatic lipid metabolism, influencing the intestinal microbiota through the liver-gut axis, and regulating systemic lipid metabolism.