Altered gut microbiota is associated with sleep disturbances in patients with minimal hepatic encephalopathy caused by hepatitis B-related liver cirrhosis

Abstract

ABSTRACT Background Sleep disturbances are prevalent in patients with minimal hepatic encephalopathy (MHE). This study aimed to evaluate the association between sleep disturbances and altered gut microbiota in patients with MHE caused by hepatitis B-related liver cirrhosis. Research design and methods Ninety-eight and 45 patients with MHE were included in exploration and validation cohorts, respectively. Sleep disturbances were assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Microbiota in fecal samples were analyzed via amplicon sequencing of bacterial 16S ribosomal RNA genes. Results The gut microbiomes of MHE patients with sleep disturbances were characterized by lower bacterial diversity and distinct bacterial composition. Relative abundances of Streptococcus salivarius and Veillonella were independent predictors of sleep disturbances in MHE patients and well-distinguished MHE patients with and without sleep disturbances in both the exploration and validation cohorts. Moreover, the relative abundances of S. salivarius were positively correlated with plasma ammonia levels, and functional modules associated with protein digestion and absorption and lipopolysaccharide biosynthesis were enriched in the microbiomes of MHE patients with sleep disturbances. Conclusions Both S. salivarius and Veillonella were associated with sleep disturbances in patients with MHE caused by hepatitis B-related liver cirrhosis.