Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation
Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation
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DOI：
10.1152/ajpgi.00152.2012
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发表时间：
2012-09-01
影响因子：
4.5
通讯作者：
Gillevet, Patrick M.
中科院分区：
文献类型：
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作者：
Bajaj, Jasmohan S.;Hylemon, Phillip B.;Gillevet, Patrick M.
尽管肝性脑病（HE）与肠道微生物群有关，但粪便微生物组分析并未发现HE和非HE患者之间的差异。本研究旨在比较肝硬化患者与对照组、肝硬化患者与非肝硬化患者的乙状结肠黏膜微生物组，并研究其与认知和炎症的联系。60例肝硬化患者（36例HE和24例非HE）接受了认知测试、粪便收集、细胞因子（Th1、Th2、Th17和先天免疫）和内毒素分析。36例患者（19例HE和17例无HE）和17例年龄匹配的对照组接受了乙状结肠活检。对粪便和粘膜进行多标签焦氧测序（包括原生属，即Blautia， Roseburia, Fecalibacterium, Dorea）。进行组内/组间粪便和粘膜微生物组差异及相关网络分析。与肝硬化患者，特别是HE患者相比，对照组有明显更高的原生和低致病性属。HE患者的终末期肝病模型MELD评分和认知能力较无HE患者差，IL-6和内毒素水平较高。HE/no-HE组的粘膜微生物群与粪便不同。在HE/非HE患者中，粪便微生物群没有差异，但粘膜微生物群存在差异，HE患者中Roseburia的丰度较低，而Enterococcus、Veillonella、Megasphaera和Burkholderia的丰度较高。在网络分析中，本地属（Blautia, Fecalibacterium， Roseburia和Dorea）在HE/ non -HE中与良好的认知和炎症减少有关，而在HE中过度代表的属（Enterococcus， Megasphaera和Burkholderia）与认知差和炎症有关。肝硬化患者乙状结肠黏膜微生物组与粪便微生物组有显著差异。肝硬化，特别是HE，患者的粘膜微生物群与对照组明显不同，缺乏潜在有益的原生菌群和潜在致病菌群的过度生长，这与认知能力低下和炎症有关。
Although hepatic encephalopathy (HE) is linked to the gut microbiota, stool microbiome analysis has not found differences between HE and no-HE patients. This study aimed to compare sigmoid mucosal microbiome of cirrhotic patients to controls, between HE vs. no-HE patients, and to study their linkage with cognition and inflammation. Sixty cirrhotic patients (36 HE and 24 no-HE) underwent cognitive testing, stool collection, cytokine (Th1, Th2, Th17, and innate immunity), and endotoxin analysis. Thirty-six patients (19 HE and 17 no-HE) and 17 age-matched controls underwent sigmoid biopsies. Multitag pyrosequencing (including autochthonous genera, i.e., Blautia, Roseburia, Fecalibacterium, Dorea) was performed on stool and mucosa. Stool and mucosal microbiome differences within/between groups and correlation network analyses were performed. Controls had significantly higher autochthonous and lower pathogenic genera compared with cirrhotic patients, especially HE patients. HE patients had worse MELD (model for end-stage liver disease) score and cognition and higher IL-6 and endotoxin than no-HE. Mucosal microbiota was different from stool within both HE/no-HE groups. Between HE/no-HE patients, there was no difference in stool microbiota but mucosal microbiome was different with lower Roseburia and higher Enterococcus, Veillonella, Megasphaera, and Burkholderia abundance in HE. On network analysis, autochthonous genera (Blautia, Fecalibacterium, Roseburia, and Dorea) were associated with good cognition and decreased inflammation in both HE/no-HE, whereas genera overrepresented in HE (Enterococcus, Megasphaera, and Burkholderia) were linked to poor cognition and inflammation. Sigmoid mucosal microbiome differs significantly from stool microbiome in cirrhosis. Cirrhotic, especially HE, patients' mucosal microbiota is significantly different from controls with a lack of potentially beneficial autochthonous and overgrowth of potentially pathogenic genera, which are associated with poor cognition and inflammation.