Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B.subtilis R-179 and E.faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. Forty mice were administered a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into the model group (group M) and three treatment groups (n = 10 per group), which were administered LCBE at 0.023 g/mouse/day (group L) or 0.230 g/mouse/day (group H), or atorvastatin 0.010 g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon Index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.

中文翻译：

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屎肠球菌 R-026 联合枯草芽孢杆菌 R-179 缓解 C57BL/6 小鼠高胆固醇血症并调节肠道微生物群

益生菌已被证明可以降低轻度高胆固醇血症患者的总胆固醇 (TC) 和低密度脂蛋白胆固醇 (LDL-C)。我们之前的研究发现，众所周知的益生菌枯草芽孢杆菌 R-179 和屎肠球菌 R-026 的干预可以通过改善肠道菌群来改善与肥胖相关的血脂异常，但迄今为止尚未有关于高胆固醇血症的类似研究报道。在这里，我们研究了活枯草芽孢杆菌 R-179 和屎肠球菌 R-026 (LCBE) 组合在高胆固醇血症 C57BL/6 小鼠模型中的治疗效果。40只小鼠被给予高胆固醇饮食（含1.2%胆固醇）以建立高胆固醇血症状态4周。然后，将小鼠分为模型组（M组）和三个治疗组（每组n = 10），以0.023 g/小鼠/天（L组）或0.230 g/小鼠/天（H组）给予LCBE ），或阿托伐他汀 0.010 g/kg/天（A 组），持续 5 周，同时采用高胆固醇饮食。高剂量LCBE显着缓解M组症状，降低血清TC、LDL-C和脂多糖（LPS）。LCBE 改善了高胆固醇饮食引起的肝脏脂肪变性和脂肪细胞增大。此外，LCBE 的施用调节了肠道微生物群和多样性的变化（香农指数）。与M组相比，治疗组Actinobacteriota、Colidextribacter和Dubosiella的相对丰度显着降低，且与血清TC和LPS呈正相关。这些发现表明 LCBE 治疗高胆固醇血症的作用机制可能是调节肠道微生物群。总之，LCBE 可改善高胆固醇血症小鼠的脂质积累、减少炎症并缓解肠道微生物群失衡。这些发现支持 LCBE 作为治疗高胆固醇血症的临床候选药物的益生菌作用。