Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease
Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease
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DOI：
10.1136/gutjnl-2016-313432
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发表时间：
2018-05-01
期刊：
影响因子：
24.5
通讯作者：
Tilg, Herbert
中科院分区：
文献类型：
--
作者：
Grander, Christoph;Adolph, Timon E.;Tilg, Herbert
目的酒精性肝病（ALD）是一个全球性的健康问题，其治疗选择有限.肠屏障完整性和微生物群调节对ALD的易感性。嗜粘蛋白阿克曼氏菌是一种革兰氏阴性肠道真菌，部分通过增强粘液产生来促进屏障功能。本研究的目的是调查ALD中的微生物改变，并确定A。设计在Lieber-DeCarli ALD小鼠模型中通过16S核糖体DNA（rDNA）测序以无偏的方法分析肠道微生物群，并且在ALD的过程中进行粪便A.在一组酒精性脂肪性肝炎（ASH）患者中测定嗜粘蛋白体丰度。A.在预防和治疗环境中确定了嗜粘蛋白菌对实验性急性和慢性ALD发展的影响，并分析了肠屏障的完整性。与健康对照相比，嗜粘蛋白性肝病与肝病严重程度间接相关。野生型小鼠的乙醇喂养导致A。粘蛋白体丰度。乙醇诱导的肠道A.口服A.嗜粘蛋白补充剂。此外，A.当在预防性环境中进行时，嗜粘蛋白的施用减少了肝损伤、脂肪变性和嗜中性粒细胞浸润。a.嗜粘蛋白菌还防止乙醇诱导的肠渗漏、增强粘液厚度和紧密连接表达。在已经建立的ALD中，A.结论酒精暴露可减少肠道嗜粘蛋白血症患者的肝损伤和中性粒细胞浸润。在小鼠和人类中，嗜粘蛋白体丰度增加，并且可以通过口服补充在实验ALD中恢复。a.嗜粘蛋白体促进肠屏障完整性并改善实验性ALD。我们的数据表明，ALD患者可能受益于A。嗜粘蛋白补充剂。
Objective A lcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD.Design The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A. muciniphila abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of A. muciniphila on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed.Results Patients with ASH exhibited a decreased abundance of faecal A. muciniphila when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in A. muciniphila abundance. Ethanol-induced intestinal A. muciniphila depletion could be restored by oral A. muciniphila supplementation. Furthermore, A. muciniphila administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. A. muciniphila also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically ameliorated hepatic injury and neutrophil infiltration.Conclusion Ethanol exposure diminishes intestinal A. muciniphila abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. A. muciniphila promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from A. muciniphila supplementation.