Linkage of gut microbiome with cognition in hepatic encephalopathy
Linkage of gut microbiome with cognition in hepatic encephalopathy
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DOI：
10.1152/ajpgi.00190.2011
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发表时间：
2012-01-01
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.;Ridlon, Jason M.;Gillevet, Patrick M.
Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, hehuman DM, Smith S, Sikaroodi M, Gillevet PM。肝性脑病患者肠道微生物群与认知的联系。[J] .中国生物医学工程学报，2012,31(2):568 - 571。首次发表于2011年9月22日；doi: 10.1152 / ajpgi.00190.2011。肝性脑病（HE）在肠屏障功能障碍的情况下与肠道细菌和炎症有关。我们的目标是使用系统生物学方法将肠道微生物组与HE中的认知和炎症联系起来。多标签焦磷酸测序（MTPS）对肝硬化患者的粪便和年龄匹配的对照组进行。肝硬化伴/不伴HE者进行认知测试、炎症细胞因子和内毒素分析。采用相关网络分析将HE患者与非HE患者进行比较。选择一组服用乳果糖的HE患者（n = 7）在乳果糖停药前后14天内进行粪便MTPS。纳入25例患者[17例HE（全部使用乳果糖，6例也使用利福昔明）和8例不使用HE，年龄56 +/- 6岁，终末期肝病模型评分16 +/- 6]和10例对照组。肝硬化患者的粪便微生物群与对照组相比存在显著差异（肠杆菌科、铝杆菌科和梭杆菌科较高，瘤胃球菌科和毛杆菌科较低）。我们发现，与没有HE的肝硬化患者相比，HE患者的菌群改变（较高的细叶藻科）、认知能力差、内毒素血症和炎症（IL-6、tnf - α、IL-2和IL-13）。肝硬化组alcaligenecae和Porphyromonadaceae与认知功能障碍呈正相关。Fusobacteriaceae、Veillonellaceae和enterobacteraceae与炎症呈正相关，Ruminococcaceae与炎症负相关。网络分析比较显示，只有在HE组中，微生物组、认知与IL-23、IL-2和IL-13之间存在显著相关性（P均< 1E-5）。除粪杆菌的减少外，乳果糖的戒断并没有显著改变微生物组。我们的结论是，与健康个体相比，肝硬化，特别是合并HE时，与粪便微生物组的显著改变有关。特定的细菌家族（Alcaligeneceae, Porphyromonadaceae, enterobacteraceae）与HE的认知和炎症密切相关。
Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol 302: G168-G175, 2012. First published September 22, 2011; doi:10.1152/ajpgi.00190.2011.-Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE (n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 +/- 6 yr, model for end-stage liver disease score 16 +/- 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae, Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae) compared with controls. We found altered flora (higher Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-alpha, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.