Propionate Ameliorates Alcohol-Induced Liver Injury in Mice via the Gut-Liver Axis: Focus on the Improvement of Intestinal Permeability
Propionate Ameliorates Alcohol-Induced Liver Injury in Mice via the Gut-Liver Axis: Focus on the Improvement of Intestinal Permeability
复制标题
丙酸通过肠-肝轴改善小鼠酒精性肝损伤：侧重于改善肠道通透性
DOI：
10.1021/acs.jafc.2c00633
复制
发表时间：
2022-05-25
影响因子：
6.1
通讯作者：
Mackay, Charles R.
中科院分区：
文献类型：
--
作者：
Xu, Qi;Zhang, Renshuai;Mackay, Charles R.
酒精相关性肝病（ALD）是全球慢性肝病的主要原因，治疗选择有限。在此，我们首次揭示了肠道微生物来源的丙酸盐对小鼠酒精性肝损伤的有益作用，这种作用依赖于调节肠-肝轴的稳态，特别是改善血管通透性。饮食中补充丙酸盐可保护小鼠免受乙醇诱导的肝功能丧失和肝脂肪变性。同时，丙酸盐治疗减轻了肠上皮屏障功能障碍，恢复了肠粘液层成分的表达，抑制了肠道炎症，改变了肠道微生物群的生态失调，从而抑制了ALD小鼠的肠道通透性过高，随后减少了脂多糖的泄漏。此外，作为内毒素血症改善的结果，肝脏炎症相关的TLR 4-NF-κ B通路被抑制。总的来说，我们的研究结果表明，丙酸补充剂可能是预防和治疗ALD的一个有前途的选择
Alcohol-related liver disease (ALD) is a major cause of chronic liver disease worldwide with limited therapeuticoptions. Here, we first revealed the promising beneficial effect of gut microbiota-derived propionate on alcoholic liver injury in mice.This effect was dependent on the modulation of homeostasis of the gut-liver axis, especially the improvement of intestinalpermeability. Dietary supplementation with propionate protected against ethanol-induced loss of hepatic function and hepaticsteatosis in mice. Meanwhile, propionate treatment attenuated intestinal epithelial barrier dysfunction, restored the expression ofintestinal mucus layer components, suppressed intestinal inflammation, and altered intestinal microbiota dysbiosis, which inhibitedthe intestinal hyperpermeability and subsequently reduced lipopolysaccharide leakage in ALD mice. Furthermore, as a consequenceof endotoxemia amelioration, the liver inflammation-related TLR4-NF-Kappa B pathway was inhibited. Collectively, our results suggested that propionate supplementation may be a promising option for the prevention and treatment of ALD