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Background: Fermented milk is beneficial for metabolic disorders, while the underlying mechanisms of action remain unclear. This study explored the benefits and underlying mechanisms of Bifidobacterium longum 070103 fermented milk (BLFM) in thirteen-week high-fat and high-sugar (HFHS) fed mice using omics techniques. Methods and results: BLFM with activated glucokinase (GK) was screened by a double-enzyme coupling method. After supplementing BLFM with 10 mL/kg BW per day, fasting blood glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and leptin were significantly reduced compared with the HFHS group. Among them, the final body weight (BW), epididymal fat, perirenal fat, and brown fat in BLFM group had better change trends than Lacticaseibacillus rhamnosus GG fermented milk (LGGFM) group. The amplicon and metabolomic data analysis identified Bifibacterium as a key gut microbiota at regulating glycolipid metabolism. BLFM reverses HFHS-induced reduction in bifidobacteria abundance. Further studies showed that BLFM significantly reduces the content of 3-indoxyl sulofphate associated with intestinal barrier damage. In addition, mice treated with BLFM improved BW, glucose tolerance, insulin resistance, and hepatic steatosis. Conclusion: BLFM consumption attenuates obesity and related symptoms in HFHS-fed mice probably via the modulation of gut microbes and metabolites.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillusparacasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.