Linkage of gut microbiome with cognition in hepatic encephalopathy

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 cog-nition, endotoxemia, and inflammation (IL-6, TNF-, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively cor-related with cognitive impairment. Fusobacteriaceae, Veillonel-laceae, and Enterobacteriaceae were positively and Ruminococ-caceae negatively related to inflammation. Network-analysis compar-ison showed robust correlations (all P 1E-5) only in the HE grou