Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis.
Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis.
复制标题
肝硬化患者肠肝脑轴受损
DOI：
10.1038/srep26800
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发表时间：
2016-05-26
影响因子：
4.6
通讯作者：
Bajaj JS
中科院分区：
文献类型：
--
作者：
Ahluwalia V;Betrapally NS;Hylemon PB;White MB;Gillevet PM;Unser AB;Fagan A;Daita K;Heuman DM;Zhou H;Sikaroodi M;Bajaj JS
肝硬化与称为肝性脑病（HE）的脑功能障碍有关。尽管已经提出了通过肠道生态失调引起的高氨血症和全身性炎症，但HE背后的机制尚不清楚。我们的目的是使用多模态MRI确定肝硬化患者中特定肠道细菌分类群对脑功能中星形胶质细胞和神经元变化的个体贡献。187名受试者（40名对照，147名癫痫患者; 87名患有HE）接受了全身炎症评估，认知测试，粪便微生物群分析和脑MRI分析。谷氨酸/谷氨酰胺增加、肌醇和胆碱减少的磁共振波谱（MRS）变化是高氨血症相关的星形胶质细胞变化，而扩散张量成像（DTI）显示神经元完整性和水肿的变化。比较了各组之间认知、MRI参数和肠道微生物群之间的联系。我们发现，与对照组和无HE的患者相比，HE患者的认知能力、全身炎症、生态失调和高血氨症明显更差。特定的微生物家族（土著类群负和肠杆菌科正）与磁共振波谱和高氨血症相关的星形胶质细胞的变化。另一方面，紫单胞菌科仅与DTI上的神经元变化相关，而与氨无关。我们的结论是，特定的肠道微生物类群与脑水肿相关的脑功能障碍的神经元和星形胶质细胞的后果。
Cirrhosis is associated with brain dysfunction known as hepatic encephalopathy (HE). The mechanisms behind HE are unclear although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. We aimed to define the individual contribution of specific gut bacterial taxa towards astrocytic and neuronal changes in brain function using multi-modal MRI in patients with cirrhosis. 187 subjects (40 controls, 147 cirrhotic; 87 with HE) underwent systemic inflammatory assessment, cognitive testing, stool microbiota analysis and brain MRI analysis. MR spectroscopy (MRS) changes of increased Glutamate/glutamine, reduced myo-inositol and choline are hyperammonemia-associated astrocytic changes, while diffusion tensor imaging (DTI) demonstrates changes in neuronal integrity and edema. Linkages between cognition, MRI parameters and gut microbiota were compared between groups. We found that HE patients had a significantly worse cognitive performance, systemic inflammation, dysbiosis and hyperammonemia compared to controls and cirrhotics without HE. Specific microbial families (autochthonous taxa negatively and Enterobacteriaceae positively) correlated with MR spectroscopy and hyperammonemia-associated astrocytic changes. On the other hand Porphyromonadaceae, were only correlated with neuronal changes on DTI without linkages with ammonia. We conclude that specific gut microbial taxa are related to neuronal and astrocytic consequences of cirrhosis-associated brain dysfunction.