Department of General Surgery (Hepatopancreatobiliary surgery), The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.
Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Academician (Expert) Workstation of Sichuan Province, Department of General Surgery (Hepatopancreatobiliary surgery), The Affiliated Hospital, Southwest Medical University, Luzhou, sichuan, 646000, China.
Mol Nutr Food Res. 2024 Jul;68(14):e2300927. doi: 10.1002/mnfr.202300927. Epub 2024 Jun 27.
While probiotics-based therapies have exhibited potential in alleviating alcohol-associated liver disease (ALD), the specific role of postbiotics derived from Lactobacillus reuteri (L. reuteri) in ALD remains elusive. This study aims to investigate the impact of postbiotics on ameliorating alcohol-induced hepatic steatosis and the underlying mechanisms.
Using network pharmacology, the study elucidates the targets and pathways impacted by postbiotics from L. reuteri, identifying the farnesoid X receptor (FXR) as a promising target for postbiotics against ALD, and lipid metabolism and alcoholism act as crucial pathways associated with postbiotics-targeting ALD. Furthermore, the study conducts histological and biochemical analyses coupled with LC/MS to evaluate the protective effects and mechanisms of postbiotics against ALD. Postbiotics may modulate bile acid metabolism in vivo by regulating FXR signaling, activating the FXR/FGF15 pathway, and influencing the enterohepatic circulation of bile acids (BAs). Subsequently, postbiotics regulate hepatic FXR activated by BAs and modulate the expression of FXR-mediated protein, including short regulatory partner (SHP) and sterol regulatory element binding protein-1c (SREBP-1c), thereby ameliorating hepatic steatosis in mice with ALD.
Postbiotics effectively alleviate ethanol-induced hepatic steatosis by regulating the FXR/SHP/SREBP-1c axis, as rigorously validated in both in vivo and in vitro.
虽然基于益生菌的疗法已显示出在缓解酒精相关性肝病（ALD）方面的潜力，但来自雷特氏乳杆菌（L. reuteri）的后生元在 ALD 中的具体作用仍不清楚。本研究旨在研究后生元对改善酒精诱导的肝脂肪变性的影响及其潜在机制。
利用网络药理学，本研究阐明了来自 L. reuteri 的后生元所影响的靶点和途径，确定法尼醇 X 受体（FXR）是后生元治疗 ALD 的有前途的靶点，脂质代谢和酒精中毒是与后生元靶向 ALD 相关的关键途径。此外，本研究还进行了组织学和生化分析，并结合 LC/MS 来评估后生元对 ALD 的保护作用和机制。后生元可能通过调节 FXR 信号转导、激活 FXR/FGF15 途径以及影响胆汁酸（BAs）的肠肝循环来调节体内胆汁酸代谢。随后，后生元调节由 BAs 激活的肝脏 FXR，并调节 FXR 介导的蛋白表达，包括短调节伙伴（SHP）和固醇调节元件结合蛋白-1c（SREBP-1c），从而改善酒精性肝病小鼠的肝脂肪变性。
后生元通过调节 FXR/SHP/SREBP-1c 轴有效缓解乙醇诱导的肝脂肪变性，这在体内和体外均得到了严格验证。
