Linkage of gut microbiome with cognition in hepatic encephalopathy

被引:424
作者
Bajaj, Jasmohan S. [1 ]
Ridlon, Jason M. [1 ,2 ]
Hylemon, Phillip B. [1 ,2 ]
Thacker, Leroy R. [3 ,4 ]
Heuman, Douglas M. [1 ]
Smith, Sean [5 ]
Sikaroodi, Masoumeh [5 ]
Gillevet, Patrick M. [5 ]
机构
[1] Virginia Commonwealth Univ, Div Gastroenterol Hepatol & Nutr, Richmond, VA 23249 USA
[2] Virginia Commonwealth Univ, Div Microbiol, Richmond, VA 23249 USA
[3] Virginia Commonwealth Univ, Div Biostat, Richmond, VA 23249 USA
[4] McGuire VA Med Ctr, Richmond, VA USA
[5] George Mason Univ, Microbiome Anal Ctr, Manassas, VA USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2012年 / 302卷 / 01期
关键词
cirrhosis; inflammation; systems biology; multitag pyrosequencing; CIRRHOTIC-PATIENTS; POSSIBLE MECHANISM; INFLAMMATION; QUANTIFICATION; DYSBIOSIS; DIAGNOSIS; LACTULOSE; BACTERIA; BEHAVIOR; THERAPY;
D O I
10.1152/ajpgi.00190.2011
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:G168 / G175
页数:8
相关论文
共 45 条
[1]   Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells [J].
Ahern, Philip P. ;
Schiering, Chris ;
Buonocore, Sofia ;
McGeachy, Mandy J. ;
Cua, Dan J. ;
Maloy, Kevin J. ;
Powrie, Fiona .
IMMUNITY, 2010, 33 (02) :279-288
[2]   Review article: the modern management of hepatic encephalopathy [J].
Bajaj, J. S. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2010, 31 (05) :537-547
[3]   Inhibitory Control Test for the Diagnosis of Minimal Hepatic Encephalopathy [J].
Bajaj, Jasmohan S. ;
Hafeezullah, Muhammad ;
Franco, Jose ;
Varma, Rajiv R. ;
Hoffmann, Raymond G. ;
Knox, Joshua F. ;
Hischke, Darrell ;
Hammeke, Thomas A. ;
Pinkerton, Steven D. ;
Saeian, Kia .
GASTROENTEROLOGY, 2008, 135 (05) :1591-1600
[4]   Rifaximin Improves Driving Simulator Performance in a Randomized Trial of Patients With Minimal Hepatic Encephalopathy [J].
Bajaj, Jasmohan S. ;
Heuman, Douglas M. ;
Wade, James B. ;
Gibson, Douglas P. ;
Saeian, Kia ;
Wegelin, Jacob A. ;
Hafeezullah, Muhammad ;
Bell, Debulon E. ;
Sterling, Richard K. ;
Stravitz, R. Todd ;
Fuchs, Michael ;
Luketic, Velimir ;
Sanyal, Arun J. .
GASTROENTEROLOGY, 2011, 140 (02) :478-U179
[5]   Persistence of Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy [J].
Bajaj, Jasmohan S. ;
Schubert, Christine M. ;
Heuman, Douglas M. ;
Wade, James B. ;
Gibson, Douglas P. ;
Topaz, Allyne ;
Saeian, Kia ;
Hafeezullah, Muhammad ;
Bell, Debulon E. ;
Sterling, Richard K. ;
Stravitz, R. Todd ;
Luketic, Velimir ;
White, Melanie B. ;
Sanyal, Arun J. .
GASTROENTEROLOGY, 2010, 138 (07) :2332-2340
[6]   Association of Proton Pump Inhibitor Therapy With Spontaneous Bacterial Peritonitis in Cirrhotic Patients With Ascites [J].
Bajaj, Jasmohan S. ;
Zadvornova, Yelena ;
Heuman, Douglas M. ;
Hafeezullah, Muhammad ;
Hoffmann, Raymond G. ;
Sanyal, Arun J. ;
Saeian, Kia .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2009, 104 (05) :1130-1134
[7]   Characterization of Fecal Microbial Communities in Patients with Liver Cirrhosis [J].
Chen, Yanfei ;
Yang, Fengling ;
Lu, Haifeng ;
Wang, Baohong ;
Chen, Yunbo ;
Lei, Dajiang ;
Wang, Yuezhu ;
Zhu, Baoli ;
Li, Lanjuan .
HEPATOLOGY, 2011, 54 (02) :562-572
[8]   New assessment of hepatic encephalopathy [J].
Cordoba, Juan .
JOURNAL OF HEPATOLOGY, 2011, 54 (05) :1030-1040
[9]   The microbiome-gut-brain axis: from bowel to behavior [J].
Cryan, J. F. ;
O'Mahony, S. M. .
NEUROGASTROENTEROLOGY AND MOTILITY, 2011, 23 (03) :187-192
[10]   Targeting IL-23 in human diseases [J].
D'Elios, Mario M. ;
Del Prete, Gianfranco ;
Amedei, Amedeo .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2010, 14 (07) :759-774