Lactobacillus rhamnosus B16 Regulates Lipid Metabolism Homeostasis by Producing Acetic Acid

Background Hyperlipidemia, a chronic disorder caused by abnormal lipid metabolism, increases risks of atherosclerosis and cardiovascular diseases. 
Current single-target drugs have limited efficacy and side effects, prompting interest in probiotics like Lactobacillus rhamnosus, though their mechanisms remain unclear.Methods A novel Lactobacillus rhamnosus strain from healthy human feces was identified via API 50CH and ANI analysis. Genomic/proteomic analyses characterized metabolic pathways. In vitro assays evaluated cholesterol degradation, gastrointestinal tolerance, and biofilm formation. Foam cell models and Western blotting assessed lipid-related proteins. A high fat diet (HFD)-induced hyperlipidemic mouse model was used for in vivo validation, with serum lipid profiling, histology, and immunohistochemistry. Metabolomic and SCFA analyses identified key metabolites, validated by sodium acetate treatment.
Results We identified a novel strain of Lactobacillus rhamnosus B16 (L. rB16) from healthy human feces, which had cholesterol-lowering ability in a high cholesterol MRS broth. Moreover, we found that heat-inactivated L. rB16 (HI-L. rB16) could reduce foam cell cholesterol levels through the LXRα signaling pathway and regulate hepatic lipid metabolism balance by regulating the expression of key lipid proteins. Metabolomics showed the acetic acid produced by L. rB16 was the main metabolite that exerted the cholesterol-lowering effect.
Conclusions L. rB16 alleviates high-fat-diet-induced hyperlipidemia in mice by reducing cholesterol through acetate-mediated LXRα signaling, demonstrating its therapeutic potential as a probiotic for lipid metabolism disorders.

背景：高脂血症（Hyperlipidemia）是一种由脂质代谢异常引发的慢性疾病，会增加动脉粥样硬化与心血管疾病的发病风险。当前单靶点药物存在疗效有限且伴随不良反应的缺陷，促使学界将目光投向鼠李糖乳杆菌（Lactobacillus rhamnosus）这类益生菌，但其发挥作用的具体机制仍未明确。
方法：本研究从健康人粪便中分离得到一株新型鼠李糖乳杆菌，通过API 50CH试剂盒与平均核苷酸一致性（ANI）分析完成菌种鉴定。采用基因组与蛋白质组分析对其代谢通路进行解析；通过体外实验评估该菌株的胆固醇降解能力、胃肠道耐受性与生物膜形成能力；利用泡沫细胞模型与蛋白质免疫印迹（Western Blotting）检测脂质相关蛋白的表达情况；构建高脂饮食（HFD）诱导的高脂血症小鼠模型开展体内验证，通过血清脂质谱分析、组织病理学检测与免疫组化分析评估干预效果；结合代谢组与短链脂肪酸（SCFA）分析筛选关键代谢物，并通过乙酸钠处理实验完成验证。
结果：本研究从健康人粪便中成功分离得到一株新型鼠李糖乳杆菌B16（L. rB16），该菌株在高胆固醇MRS培养基中展现出降胆固醇活性。此外，研究发现热灭活的L. rB16（HI-L. rB16）可通过肝X受体α（LXRα）信号通路降低泡沫细胞内胆固醇水平，并通过调控关键脂质蛋白的表达维持肝脏脂质代谢平衡。代谢组学分析显示，L. rB16产生的乙酸是介导其降胆固醇作用的核心代谢物。
结论：L. rB16可通过乙酸介导的LXRα信号通路降低胆固醇水平，从而缓解高脂饮食诱导的小鼠高脂血症，证实其作为治疗脂质代谢紊乱的益生菌候选菌株具有潜在治疗价值。