Mun Daye, Ryu Sangdon, Lee Daniel Junpyo, Kwak Min-Jin, Choi Hyejin, Kang An Na, Lim Dong-Hyun, Oh Sangnam, Kim Younghoon
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, 08826, Republic of Korea.
Honam National Institute of Biological Resources, Mokpo, 58762, Republic of Korea.
Curr Res Food Sci. 2025 Mar 25;10:101039. doi: 10.1016/j.crfs.2025.101039. eCollection 2025.
Non-alcoholic steatohepatitis (NASH), characterized by severe fatty liver-associated inflammation and hepatocellular damage, is a major precursor to cirrhosis and hepatocellular carcinoma. While the exact pathogenesis of NASH remains unclear, gut microbiota dysbiosis has been implicated as a key factor contributing to endotoxin translocation and chronic liver inflammation. Recent studies have highlighted the therapeutic potential of bovine colostrum-derived extracellular vesicles (BCEVs) in modulating gut microbiota and enhancing gut barrier function, but their effects on NASH remain largely unexplored. To investigate the potential protective effects of BCEVs against NASH, 8-wk-old mice were fed a NASH-inducing diet for 3 wks while concurrently receiving oral BCEV administration. BCEV treatment markedly ameliorated hepatic steatosis, fibrosis, and inflammation. Transcriptomic analyses demonstrated a notable reduction in lipid metabolism, bacterial response, and inflammatory pathways in the intestine, as well as reduced expression of inflammation- and fibrosis-related pathways in the liver. Gut microbiota profiling revealed an increased abundance of , accompanied by enhanced cholesterol excretion. Furthermore, BCEV treatment promoted the production of tight junction proteins and mucin in the gut, reinforcing intestinal barrier integrity. These findings suggest that BCEVs promote the proliferation of , which in turn prevents endotoxin translocation to the liver. This reduction in endotoxin leakage alleviates hepatic inflammation and fibrosis. Overall, this study highlights the therapeutic potential of BCEVs as a novel strategy for managing NASH by targeting the gut-liver axis through the modulation of gut microbiota and barrier function.
非酒精性脂肪性肝炎(NASH)以严重的脂肪肝相关炎症和肝细胞损伤为特征,是肝硬化和肝细胞癌的主要前驱病变。虽然NASH的确切发病机制尚不清楚,但肠道微生物群失调被认为是导致内毒素移位和慢性肝脏炎症的关键因素。最近的研究强调了牛初乳来源的细胞外囊泡(BCEV)在调节肠道微生物群和增强肠道屏障功能方面的治疗潜力,但其对NASH的影响在很大程度上仍未得到探索。为了研究BCEV对NASH的潜在保护作用,给8周龄小鼠喂食诱导NASH的饮食3周,同时口服BCEV。BCEV治疗显著改善了肝脏脂肪变性、纤维化和炎症。转录组分析表明,肠道中脂质代谢、细菌反应和炎症途径显著减少,肝脏中炎症和纤维化相关途径的表达也降低。肠道微生物群分析显示, 丰度增加,同时胆固醇排泄增强。此外,BCEV治疗促进了肠道中紧密连接蛋白和粘蛋白的产生,加强了肠道屏障的完整性。这些发现表明,BCEV促进了 的增殖,进而防止内毒素移位至肝脏。内毒素泄漏的减少减轻了肝脏炎症和纤维化。总体而言,本研究强调了BCEV作为一种通过调节肠道微生物群和屏障功能靶向肠-肝轴来管理NASH的新策略的治疗潜力。
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