Objective A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls.
Design We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing.
Results A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae.
Conclusions This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.
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RT, YW and YL joint first coauthorship
RT, MEG and XM joint last coauthorship
Contributors XM, MEG and RT designed and supervised the project. XM, J-YF and RT obtained funding. QW, FY, QM and DQ performed clinical diagnosis and treatment. YW, YL, WC, QC and ZF collected samples. YW, YL, ML, XJ and JZ contributed to data collection. RT, YW, YL and MW performed bioinformatics and statistical analysis, and interpreted data. RT, YW and YL drafted the manuscript. XM, MEG and AA revised the manuscript for important content.
Funding This work was supported by the National Natural Science Foundation of China grants (# 81325002 and 81620108002 to XM; #81421001 to J-YF; # 81400608 and 81570469 to RT); the Innovation Program of Shanghai Jiao Tong University grant (# YG2014MS43 to RT) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (#20161311 to RT).
Competing interests None declared.
Ethics approval Renji Hospital, School of Medicine, Shanghai Jiao Tong University.
Provenance and peer review Not commissioned; externally peer reviewed.
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