Wang Chongyu, Chen Xi, Wang Fei, Chen Tianyu, Yin Mengqiu, Liu Ziyu, Li Weifen, Zhu Jinhui
Department of General Surgery, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.
Key Laboratory of Animal Molecular Nutrition of Education of Ministry, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Animal Nutrition and Feed Sciences, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Nutrients. 2025 Jul 17;17(14):2340. doi: 10.3390/nu17142340.
Alcohol-associated liver disease (ALD) is characterized by gut-liver axis dysfunction and metabolic dysregulation, yet the therapeutic potential of probiotics remains underexplored. This study aimed to investigate the protective effects and mechanisms of 36 (LP36) against ethanol-induced ALD in mice.
Mice were pretreated with LP36 prior to ethanol exposure. Liver injury was assessed through serum ALT/AST levels, hepatic steatosis (TC/TG content), and ethanol detoxification capacity (ADH/ALDH activity). Intestinal barrier integrity was evaluated via Mucin2 and ZO-1 expression, and gut microbiota alterations were analyzed by 16S rRNA sequencing. Hepatic transcriptomics (RNA-seq) was performed to identify key regulatory pathways.
LP36 significantly attenuated ethanol-induced liver injury, evidenced by reduced ALT/AST, improved hepatic steatosis (lower TC/TG), and enhanced ADH/ALDH activity. Mechanistically, LP36 restored intestinal barrier function (upregulated Mucin2 and ZO-1), modulated gut microbiota (suppressed , , and ; enriched and ), and reduced systemic inflammation. Transcriptomics revealed LP36-mediated rescue of AMPK signaling, involving regulation of , , lipid synthesis genes (, ), and metabolic modulators (, , , ).
LP36 ameliorates ethanol-induced ALD by enhancing intestinal barrier integrity, reshaping gut microbiota, and restoring AMPK-dependent metabolic homeostasis. These findings highlight LP36 as a promising probiotic candidate for ALD prevention.
酒精性肝病（ALD）的特征是肠-肝轴功能障碍和代谢失调，然而益生菌的治疗潜力仍未得到充分探索。本研究旨在探讨36株罗伊氏乳杆菌（LP36）对小鼠乙醇诱导的ALD的保护作用及其机制。
在乙醇暴露前用LP36预处理小鼠。通过血清谷丙转氨酶/谷草转氨酶水平、肝脏脂肪变性（总胆固醇/甘油三酯含量）和乙醇解毒能力（乙醇脱氢酶/乙醛脱氢酶活性）评估肝损伤。通过黏蛋白2和紧密连接蛋白1的表达评估肠道屏障完整性，并通过16S核糖体RNA测序分析肠道微生物群的变化。进行肝脏转录组学（RNA测序）以确定关键调控途径。
LP36显著减轻了乙醇诱导的肝损伤，表现为谷丙转氨酶/谷草转氨酶降低、肝脏脂肪变性改善（总胆固醇/甘油三酯降低）以及乙醇脱氢酶/乙醛脱氢酶活性增强。机制上，LP36恢复了肠道屏障功能（上调黏蛋白2和紧密连接蛋白1），调节了肠道微生物群（抑制了 、 和 ；富集了 和 ），并减轻了全身炎症。转录组学显示LP36介导了AMPK信号通路的挽救，涉及对 、 、脂质合成基因（ 、 ）和代谢调节剂（ 、 、 ）的调控。
LP36通过增强肠道屏障完整性、重塑肠道微生物群和恢复AMPK依赖的代谢稳态来改善乙醇诱导的ALD。这些发现突出了LP36作为一种有前途的预防ALD的益生菌候选物。
