Data Sheet 6_Lactobacillus rhamnosus GG attenuates MASLD/MASH progression by modulating gut microbiota and metabolic pathways.zip

IntroductionNon-alcoholic fatty liver disease (MASLD) is a common liver condition with a global prevalence of approximately 25%, often associated with overweight, obesity, and abnormalities in glucose and lipid metabolism. Its histological hallmark is hepatic steatosis. Non-alcoholic steatohepatitis (MASH), an advanced form of MASLD, can lead to cirrhosis and liver cancer. Dysbiosis of the gut microbiota plays a significant role in chronic liver diseases, making probiotic treatment a focal point in MASLD research. Studies have shown that Lactobacillus rhamnosus GG (LGG) can improve gut microbiota, reduce hepatic fat accumulation, and lower blood lipid levels in MASLD model mice. However, the role of LGG in the progression from MASLD to MASH remains unclear. MethodsIn this study, we constructed MASLD and MASH models using a high-fructose, high-fat diet combined with carbon tetrachloride (CCl4) induction to explore the effects of LGG on disease progression. Our findings revealed that in the MASLD model, LGG improved lipid metabolism and inflammatory responses by modulating the gut microbiota (e.g., increasing the abundance of Bacteroidetes) and promoting the production of short-chain fatty acids (SCFAs). Additionally, LGG reduced the expression of genes related to lipogenesis, further alleviating MASLD. ResultsIn the MASH model, LGG primarily exerted its effects by inhibiting the TGF-β/SMAD signaling pathway and reducing the expression of pro-inflammatory factors (e.g., IL-1β, IL-6, TNF-α), thereby mitigating liver fibrosis and inflammation. Furthermore, LGG restored intestinal barrier function, reduced intestinal permeability, and prevented harmful substances like endotoxins from entering the liver, further alleviating hepatic inflammation and fibrosis. DiscussionAlthough LGG shows promise in the treatment of MASLD and MASH, its mechanisms of action and long-term effects require further investigation. Future research should focus on optimizing the types, dosages, and treatment regimens of probiotics, as well as monitoring their long-term impact on gut microbiota balance, to ensure their safety and efficacy in clinical applications.引言 非酒精性脂肪性肝病（Non-alcoholic fatty liver disease, MASLD）是一种常见肝脏疾病，全球患病率约为25%，常与超重、肥胖及糖脂代谢异常相关。其组织学特征为肝脏脂肪变性。非酒精性脂肪性肝炎（Non-alcoholic steatohepatitis, MASH）作为MASLD的进展型亚型，可进展为肝硬化及肝细胞癌。肠道菌群失调在慢性肝病中发挥重要作用，因此益生菌治疗成为MASLD研究的热点方向。已有研究表明，鼠李糖乳杆菌GG（Lactobacillus rhamnosus GG, LGG）可改善MASLD模型小鼠的肠道菌群，减轻肝脏脂肪蓄积并降低血脂水平。但LGG在MASLD向MASH进展过程中的作用仍不明确。 方法 本研究采用高果糖高脂膳食联合四氯化碳（carbon tetrachloride, CCl4）诱导构建MASLD及MASH模型，探究LGG对疾病进展的影响。研究结果显示，在MASLD模型中，LGG可通过调控肠道菌群（如增加拟杆菌门丰度）、促进短链脂肪酸（short-chain fatty acids, SCFAs）生成，改善脂代谢与炎症应答；此外，LGG可下调脂肪生成相关基因的表达，进一步缓解MASLD病变。 结果 在MASH模型中，LGG主要通过转化生长因子-β/SMAD（TGF-β/SMAD）信号通路抑制炎症及纤维化进程，下调促炎因子（如IL-1β、IL-6、TNF-α）的表达，从而减轻肝脏纤维化与炎症损伤。此外，LGG可修复肠屏障功能、降低肠道通透性，阻止内毒素等有害物质侵入肝脏，进一步缓解肝脏炎症与纤维化。 讨论 尽管LGG在MASLD及MASH的治疗中展现出应用潜力，但其具体作用机制与长期效应仍需进一步研究。未来研究应聚焦于优化益生菌的菌株类型、给药剂量与治疗方案，同时监测其对肠道菌群平衡的长期影响，以确保其临床应用的安全性与有效性。