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

Abstract

ObjectiveThe 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.DesignBile 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.ResultsThe 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.ConclusionsOur 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.

Review article: the evidence that vancomycin is a therapeutic option for primary sclerosing cholangitis

“…In contrast, patients with PSC have marked reductions in Clostridiales II , Prevotella and Roseburia , and Bacteroides , compared to patients with IBD alone and healthy controls . Actinobacteria, Proteobacteria, Streptococcus and Rothia have been reported to be overrepresented in patients with PSC compared with healthy controls and patients with inflammatory bowel disease . Mucosa‐associated bacteria as opposed to stool was also found with a lower bacterial diversity in patients with PSC, with an underrepresentation of an uncultured Clostriadiales II .…”

Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis

“…27,29 Changes have also been shown in biliary microbiota in this condition. 30 Viral hepatitis: Hepatitis B and hepatitis C have variable impact on gut microbial composition. Studies of HCV-associated liver disease on the microbiota are not very clear with results suggesting that the microbiota changes before cirrhosis and after cirrhosis.…”

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

“…Taken together, this hypothetical vicious cycle suggests a new pathogenic mechanism for antibodies encompassing features of types 2 and 3 of hypersensitive immune reactions in accordance with the classification of Coombs and Gell by involving microbiota (coloured oval area). (Adapted according to [62]) [136,137]. A possible involvement of the microbiota in PSC could also be supported by the identification of a genetic polymorphism linked with PSC as well as CD that generated a dysfunctional fucusyltransferase-2 (FUT2) [138,139].…”

“…In PSC, clinical trials demonstrated a beneficial effect of antibiosis on liver enzyme levels [146]. The aetiology of PSC does not appear to be associated with specific changes in biliary microbial communities [136]. However, the genus Streptococcus is considered to play a putative role in the progression of PSC.…”