The role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial. N-3 PUFA oxidation in animal feeding stuffs was rarely concerned, likely contributing to inconsistent outcomes. Here, we report the impacts of oxidized fish oil (OFO) on ALD in C57BL/6 mice. Alcohol exposure increased plasma aminotransferase levels and hepatic inflammation. These deleterious effects were ameliorated by unoxidized FO but exacerbated by OFO. Sequencing analysis showed the accentuated intestinal dysbiosis and the increased proportion of Proteobacteria in OFO-fed mice. Intestinal sterilization by antibiotics completely abolished OFO-aggravated liver injury. Additionally, alcohol exposure leads to the greater increase in plasma endotoxin and decrease in intestinal tight junction protein expressions in OFO-fed mice. Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin.

n-3 多不饱和脂肪酸 (PUFA) 在酒精性肝病 (ALD) 中的作用一直存在争议。动物饲料中的 N-3 PUFA 氧化很少受到关注，这可能导致结果不一致。在这里，我们报告了氧化鱼油 (OFO) 对 C57BL/6 小鼠 ALD 的影响。酒精暴露会增加血浆转氨酶水平和肝脏炎症。这些有害影响被未氧化的 FO 改善，但被 OFO 加剧。测序分析显示肠道菌群失调加剧，变形菌比例增加在 OFO 喂养的小鼠中。用抗生素进行肠道消毒完全消除了 OFO 加重的肝损伤。此外，酒精暴露导致 OFO 喂养的小鼠血浆内毒素的更大增加和肠道紧密连接蛋白表达的减少。奥贝胆酸对肠道屏障的稳定作用显着减弱了酒精喂养小鼠中 OFO 加重的肝损伤。这些结果表明，OFO 通过增强肠源性内毒素介导的肠道生态失调、屏障功能障碍和肝脏炎症，从而加剧酒精性肝损伤。