Dysbiosis of the faecal and biliary microbiotas in biliary tract cancer

Background Characteristic bile duct and colonic microbiotas have been identified in patients with chronic biliary tract disease. Therefore, a characteristic microbiota is likely also formed in cholangio- and gallbladder carcinoma patients. This study aimed to characterize the faecal and bile microbiotas in biliary tract cancer (BTC) patients and their relationship to each other. Methods Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were prospectively included. Ten healthy, age-matched subjects were also recruited for faecal microbiota comparison. The colon and bile duct microbiotas were analysed by sequencing the 16S rRNA gene V3-V4 region. We also obtained live bacteria in the bile collected from three BTC patients by culture and performed metagenomics-based identification. Results The faecal microbiota composition differed in the BTC patients. Linear discriminant analysis (LDA) effect size (LEfSe) showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of butyrate-producing bacteria including Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Notably, 10 of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile samples were matched with the OTUs found in the BTC subject faecal samples. Further metagenomic approaches revealed a bile-isolated strain that possessed the carcinogenic bacterial colipolyketide synthase (PKS)-encoding gene. Conclusions Enterobacteriaceae was enriched in the BTC faeces. Taken together with the finding that more than half of Enterobacteriaceae in the bile matched that in the faeces at the OTU level, our data suggest that faecal microbiota dysbiosis possibly contributes to BTC onset.