Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD

Abstract

ObjectivePrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often leading to end-stage liver disease. Its pathogenesis remains largely unknown, although frequent concomitant IBD hints towards common factors underlying gut and bile duct inflammation. Considering the mounting evidence on the involvement of the intestinal microbiota in initiating and determining IBD phenotype, we investigated intestinal microbiota composition in patients with PSC.DesignStool samples were collected from 147 individuals (52 patients with PSC, 52 age, gender and body mass index-matched healthy volunteers, 13 UC and 30 patients with Crohn's disease). An independent validation cohort of 14 PSC and 14 matched controls was recruited. 16S rDNA sequencing of faecal DNA was performed (Illumina MiSeq).ResultsThe microbiota of patients with PSC was characterised by decreased microbiota diversity, and a significant overrepresentation of Enterococcus (p=3.76e-05), Fusobacterium (p=3.76e-05) and Lactobacillus (p=0.0002) genera. This dysbiosis was present in patients with PSC with and without concomitant IBD and was distinct from IBD, and independent of treatment with ursodeoxycholic acid. A decision tree based on abundances of these three genera allowed reliable classification in the validation cohort. In particular, one operational taxonomic unit belonging to the Enterococcus genus was associated with increased levels of serum alkaline phosphatase (p=0.048), a marker of disease severity.ConclusionsWe here present the first report of PSC-associated faecal dysbiosis, independent from IBD signatures, suggesting the intestinal microbiota could be a contributing factor in PSC pathogenesis. Further studies are needed to confirm these findings and assess causality.

Gut microbiome and liver diseases

“…In summary, this first PSC study observed a clear gut signature in PSC distinct from healthy controls and patients with UC without liver disease suggesting that the intestinal microbiota (IM) could reflect a relevant player in PSC. These findings are strengthened by another recently published study where authors also observed an increase in Veilonella species 62 . Veilonella has been associated with other chronic inflammatory disorders including fibrotic conditions and liver cirrhosis where subjects have higher colonic Veilonella levels 63.…”

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

“…13 In summary, in this exploratory study, patients with PSC-IBD had a distinct stool BA and stool microbiota composition, as well as specific microbiota-stool BA correlations when compared with IBD. Whether these changes are associated with or may predispose to the specific PSC-IBD phenotype including the increased risk of colorectal neoplasia needs to be further clarified and warrants further research.…”

Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy

“…Murine model studies of type I diabetes indicate that gender bias may be influenced by the gut microbial community through its interaction with sex hormones, although the underlying mechanisms are poorly characterised 38 39. In contrary to PBC, no significant difference in gut microbiome has been observed between patients with PSC taking UDCA and those not 14. This coincides with the distinct therapeutic efficacy of UDCA in PBC and PSC.…”