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Objective  The etiopathogenesis and risk for development of biliary neoplasia in primary sclerosing cholangitis (PSC) are largely unknown. Microbes or their metabolites have been suggested to play a role. To explore this potential microbial involvement, we evaluated the differences in biliary microbiota in PSC patients at an early disease stage without previous endoscopic retrograde cholangiography (ERC) examinations, advanced disease stage, and with biliary dysplasia or cholangiocarcinoma.    Design  Bile samples from the common bile duct were collected from 46 controls and 80 patients with PSC during ERC (37 with early disease, 32 with advanced disease, and 11 with biliary dysplasia). DNA isolation, amplification, and Illumina MiSeq sequencing were performed for the V1-V3 regions of the bacterial 16S rRNA gene.    Results  The most common phyla found were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria. The most common families were Prevotellaceae, Streptococcaceae, Veillonellaceae, Fusobacteriaceae, and Pasteurellaceae, and the most common genera were  Prevotella ,  Streptococcus ,  Veillonella ,  Fusobacterium , and  Haemophilus . The bacterial communities of non-PSC subjects and early stage PSC patients were similar. Alpha diversity was lower in patients with biliary dysplasia/cholangiocarcinoma than in other groups. An increase in  Streptococcus  abundance was positively correlated with the number of ERC examinations.  Streptococcus  abundance was also positively correlated with an increase in disease severity, even after controlling for the number of ERC examinations.    Conclusions  Our findings suggest that the aetiology of PSC is not associated with changes in bile microbial communities, but the genus  Streptococcus  may play a pathogenic role in the progression of the disease.

Bile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia