Alteration of the gut microbiota in patients with primary sclerosing cholangitis and concomitant dominant strictures

Question:

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often leading to end-stage liver disease. Its pathogenesis remains largely unknown, although frequent concomitant inflammatory bowel disease (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 and compared it to patients with IBD.

Methods:

Stool samples of patients with PSC (n = 49) were collected and compared with samples derived from IBD patients (n = 56) during the time period July 2016 till November 2018 at the University Hospital Heidelberg. At the time of collection all patients were in stable clinical condition without overt signs of infection and without antibiotic treatment for at least three month. Samples were prepared for DNA-isolation and sequenced by ILUMINASeq method. In PSC patients subgroups depending on the presence of dominant strictures (DS) or IBD were analyzed. Clinical and laboratory data were collected by chart review.

Results:

The alpha-diversity is significantly higher in PSC patients due to a more rich microbiome while the dominance is not significantly different. We also observed a significant change in the structure of the microbiome (R²= 2%; p-value: 0.016). This change is due to a significant decrease of Firmicutes and increase of Bacteroides in the PSC group. There was no influence of the underlying IBD on the structure. However, the alpha diversity was significantly increased in patients with PSC only compared to PSC patients with concomitant CU (p < 0.01) and CD (p < 0.05) indicating a strong effect of the underlying disease on the microbiome. In subgroup analyis of PSC patients with DS we observed no major impact of the stricture on the alpha and beta-diversity level indicating no changes in the overall structure of the microbiome. There was was a slight change in the structure (R²= 0.05, p-value = 0.012) and several species showed a significant difference related to the presence of stricture indicating a mild effect on the biosphere of the microbiome.

Conclusion:

Gut microbiota composition in PSC patients showes disease specific alterations compared to IBD patients. Differences in the colonic microbiome depending on concomitant IBD or the presence of DS in PSC might be a contributing factor in PSC pathogenesis.