Enterococcus hirae WEHI01 is a potential probiotic strain isolated from a healthy Chinese infant. This strain has previously been characterized as having cholesterol-lowering potential and good dairy fermentation performance. In this study, we used rat models with obesity and type 2 diabetes mellitus (T2DM) induced by a high fat and sucrose diet and low-dose streptozotocin, respectively, and we evaluated the effect of E. hirae WEHI01 on glycolipid metabolism, glycolipid-related gene expression,

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... organ histopathology, and intestinal flora changes in the 2 models. Our results showed that administration of 5.0 × 109 cfu of E. hirae WEHI01 for 4 wk decreased serum lipid levels and regulated glycolipid metabolism in the liver of obese rats. Following continuous administration of the same concentration of E. hirae WEHI01 to a T2DM rat model for another 5 wk, E. hirae WEHI01 improved glucose tolerance, recovered body weight loss, and led to significant decreases in tumor necrosis factor-α, IL-6, IL-10, and total bile acid in serum. We also found that E. hirae WEHI01 restored the morphology of the pancreas, kidney, and liver, and changed the composition of the gut microbiota (i.e., decreased the Shannon index, increased the Simpson index, and substantially increased the abundance of Lactobacillales). Combining the results for the obese model and the T2DM model, we speculated that beneficial effects of E. hirae WEHI01 on T2DM could be due to (1) a significant increase in PPARA expression and a tendency for increased CYP7A1 expression in the liver of obese rats, promoting the conversion of cholesterol into bile acid and reducing serum total bile acid levels in T2DM model rats; or (2) a change in gut microbial diversity, especially elevated Lactobacillales abundance, which reduced the total bile acid in T2DM model rats. These results demonstrated that E. hirae WEHI01 has the potential to ameliorate type 2 diabetes in rats and provide a promising rationale for further research into the prevention and treatment of T2DM.