Kirpich Irina A, Petrosino Joseph, Ajami Nadim, Feng Wenke, Wang Yuhua, Liu Yanlong, Beier Juliane I, Barve Shirish S, Yin Xinmin, Wei Xiaoli, Zhang Xiang, McClain Craig J
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
Baylor Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas.
Am J Pathol. 2016 Apr;186(4):765-76. doi: 10.1016/j.ajpath.2015.11.017.
Alcoholic liver disease (ALD) ranks among major causes of morbidity and mortality. Diet and crosstalk between the gut and liver are important determinants of ALD. We evaluated the effects of different types of dietary fat and ethanol on the gut microbiota composition and metabolic activity and the effect of these changes on liver injury in ALD. Compared with ethanol and a saturated fat diet (medium chain triglycerides enriched), an unsaturated fat diet (corn oil enriched) exacerbated ethanol-induced endotoxemia, liver steatosis, and injury. Major alterations in gut microbiota, including a reduction in Bacteroidetes and an increase in Proteobacteria and Actinobacteria, were seen in animals fed an unsaturated fat diet and ethanol but not a saturated fat diet and ethanol. Compared with a saturated fat diet and ethanol, an unsaturated fat diet and ethanol caused major fecal metabolomic changes. Moreover, a decrease in certain fecal amino acids was noted in both alcohol-fed groups. These data support an important role of dietary lipids in ALD pathogenesis and provide insight into mechanisms of ALD development. A diet enriched in unsaturated fats enhanced alcohol-induced liver injury and caused major fecal metagenomic and metabolomic changes that may play an etiologic role in observed liver injury. Dietary lipids can potentially serve as inexpensive interventions for the prevention and treatment of ALD.
酒精性肝病（ALD）是发病和死亡的主要原因之一。饮食以及肠道与肝脏之间的相互作用是ALD的重要决定因素。我们评估了不同类型的膳食脂肪和乙醇对肠道微生物群组成和代谢活性的影响，以及这些变化对ALD肝损伤的影响。与乙醇和饱和脂肪饮食（富含中链甘油三酯）相比，不饱和脂肪饮食（富含玉米油）加剧了乙醇诱导的内毒素血症、肝脏脂肪变性和损伤。在喂食不饱和脂肪饮食和乙醇的动物中，观察到肠道微生物群的主要变化，包括拟杆菌减少，变形菌和放线菌增加，而喂食饱和脂肪饮食和乙醇的动物则未出现这种情况。与饱和脂肪饮食和乙醇相比，不饱和脂肪饮食和乙醇引起了粪便代谢组学的主要变化。此外，在两个酒精喂养组中均注意到某些粪便氨基酸减少。这些数据支持膳食脂质在ALD发病机制中的重要作用，并为ALD发展的机制提供了见解。富含不饱和脂肪的饮食会加剧酒精诱导的肝损伤，并引起主要的粪便宏基因组学和代谢组学变化，这些变化可能在观察到的肝损伤中起病因学作用。膳食脂质有可能作为预防和治疗ALD的廉价干预措施。
