Preliminary study on abundance and diversity of microbiota in liver tissues of patients with autoimmune liver disease

Abstract

Objective To provide clues for the study on the mechanism of autoimmune liver disease (AILD) by exploring the existence of specific bacteria in liver tissues of AILD patients. Methods From August 2017 to August 2018, at Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, a total of 12 patients diagnosed as AILD (four autoimmune hepatitis (AIH), four primary biliary cirrhosis (PBC) and four PBC-AIH overlap syndrome (OS)) and four patients with hepatic cyst (control group) were enrolled and all the patients underwent liver biopsy. 16S rRNA gene sequencing was carried out in the obtained aseptic liver tissues. Linear discriminant analysis effect size was used to find out the specific bacteria. Spearman correlation analysis was performed to analyze the correlation between the liver microbiota and the disease. The metabolic function of the 16S rRNA gene sequences was also predicted. Results Bacteria were detected in the liver tissues of all the 16 patients. At the species level, the abundance of Planococcus rifietoensis of AIH group was 0.100%, which was higher than those of other three groups (0), and the difference was statistically significant (linear discriminant analysis (LDA)=3.31, P=0.034). The abundance of Anoxybacillus flavithermus of PBC group was 0.200%, which was higher than those of other three groups (0.100%), and the difference was statistically significant (LDA=3.34, P=0.014). The abundance of Pseudomonas aeruginosa PAO1, Bacillus firmus, Brevibacillus agri, Acinetobacter baumannii, Sphingomonas zeae and Salmonella enterica were significantly negatively correlated with serum level of γ-glutamyl transferase (r=-0.68, -0.68, -0.67, -0.68, -0.68 and -0.66, all P<0.01). Compared with that of the hepatic cyst group, the lipid metabolism of AILD patients decreased. The levels of serum low density lipoprotein and total cholesterol were significantly negatively correlated with the biosynthesis of unsaturated fatty acids (r=-0.55 and -0.65, both P<0.05). Conclusions There exist specific bacteria in the liver tissues of AIH and PBC groups. The liver microbiota which is closely related with the pathogenesis of AILD might be a potential therapeutic target and diagnostic biomarker. Key words: Autoimmune liver disease; Liver tissues; 16S rRNA gene sequencing; Microbiota richness; Diversity