J Clin Invest:肠道真菌对酒精肝的发展有推进作用

2017-07-07 MedSci MedSci原创

在美国,慢性肝病伴随肝硬化是位居第12位的致死因素,而肝硬化所致死亡中酒精肝病约占一半比例。长期酒精摄入与肠道菌失调相关,然而我们对肠道真菌或真菌区系在酒精肝病中发挥的作用知之甚少。

在美国,慢性肝病伴随肝硬化是位居第12位的致死因素,而肝硬化所致死亡中酒精肝病约占一半比例。长期酒精摄入与肠道菌失调相关,然而我们对肠道真菌或真菌区系在酒精肝病中发挥的作用知之甚少。本研究显示小鼠长期摄入酒精后,真菌种群扩大,且真菌的β-葡聚糖向系统循环的移位增加。向小鼠投喂抗真菌制剂,减少了肠道真菌过度增殖,降低β-葡聚糖的移位,并缓解酒精引起的肝病。使用骨髓嵌合小鼠发现,β-葡聚糖通过枯否细胞或可能是其他骨髓源细胞上的C型凝集素样受体CLEC7A诱导肝炎。随之而来的IL-1β的表达增加和分泌导致干细胞损伤,并促进酒精引起的肝病的发展。研究发现酒精依赖的病人肠道真菌多样性降低,同时假丝酵母过度生长。与健康人以及非酒精相关肝硬化的病人相比,酒精肝硬化病人对真菌的系统暴露及免疫响应增加。而且,肠外暴露水平和免疫响应与死亡率相关。如此看来,长期摄入酒精会出现真菌种群改变及真菌产物移位等症状。调控肠道真菌群或许是缓解酒精相关肝疾病的有效措施。

原始出处:
An-Ming Yang, et al. Intestinal fungi contribute to development of alcoholic liver disease. J Clin Invest. 2017, May.doi:10.1172/JCI90562.

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    2017-07-09 zhaojie88
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    2017-07-09 zzc2215

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