From the Department of Infectious Diseases, Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.
Department of Medicine, University of California San Diego, La Jolla, California, USA.
Alcohol Clin Exp Res. 2020 Sep;44(9):1842-1851. doi: 10.1111/acer.14405. Epub 2020 Aug 2.
Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease.
Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model).
Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice.
Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.
肠道 α1-2-岩藻糖基转移酶 2（Fut2）介导的肠道 α1-2-岩藻糖基化在维持共生宿主-微生物群关系中很重要，并且可以预防几种病原体。肠道菌群失调是实验性乙醇（EtOH）诱导的肝病进展的一个重要因素，但 Fut2 在调节酒精相关肝病期间肠道糖萼中的作用尚不清楚。我们研究了 Fut2 介导的肠道 α1-2-岩藻糖基化在酒精相关肝病发展中的作用。
应用免疫组织化学染色法评估酒精使用障碍患者十二指肠活检中的 α1-2-岩藻糖基化。野生型（WT）和 Fut2 缺陷型同窝仔鼠接受 Lieber-DeCarli 慢性 EtOH 给药模型和慢性 binge EtOH 饮食（NIAAA 模型）。
酒精使用障碍患者的肠道 α1-2-岩藻糖基化下调。Fut2 缺陷型小鼠缺乏 α1-2-岩藻糖基化会加剧慢性 EtOH 诱导的肝损伤、脂肪变性和炎症，而不影响 EtOH 代谢。在 NIAAA 模型中，饮食补充 α1-2-岩藻糖化聚糖 2'-岩藻糖基乳糖（2'-FL）可改善 Fut2 缺陷型小鼠的 EtOH 诱导的肝病。尽管 2'-FL 对体外粪肠球菌的生长没有直接影响，但肠道 α1-2-岩藻糖基化可减少 EtOH 喂养小鼠肠道中细胞溶素阳性粪肠球菌的定植。
肠道 α1-2-岩藻糖基化是一种针对 EtOH 诱导的肝病的宿主保护机制。2'-FL 是一种天然存在于人乳中的寡糖，可被视为治疗酒精相关肝病的药物。
