Primary Sclerosing Cholangitis Characterized By Intestinal Dysbiosis

Primary Sclerosing Cholangitis also known as PSC, is a liver disease with no effective medical treatment and liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will ultimately require it.

The vast majority of patients with PSC also have inflammatory bowel disease, either Crohn's disease or ulcerative colitis (UC), possibly implying that the intestine plays a role in the origin of this PSC. The pathogenesis of PSC remains poorly understood, with current evidence suggesting that genetic, immunologic and environmental factors all play a role.

Scientists at the University of Leuven (Belgium) collected fresh fecal samples 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. Blood samples were taken during the same clinic visit.

Fecal calprotectin measurements were performed for all patients with the fCAL enzyme-linked immunosorbent assay (ELISA) kit (Bühlmann Laboratories, Schönenbuch, Switzerland). Fecal calprotectin was not quantified in healthy controls and in patients with UC because samples were frozen on collection, which may result in overestimation. The team performed 16S rDNA sequencing of fecal DNA using a MiSeq desktop sequencer (Illumina, San Diego, CA, USA).

The scientists found that the microbiota of patients with PSC was characterized by decreased microbiota diversity, and a significant overrepresentation of Enterococcus, Fusobacterium and Lactobacillus 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 a marker of disease severity.

Jeroen Raes, PhD, a professor and senior author of the study, said, “Using massive DNA sequencing, we compared the gut bacteria in patients with PSC and in healthy people. Based on the differences found, we could develop a signature to diagnose PSC based on gut bacteria. Although very promising, our findings now need to be confirmed before they can be used in clinical practice.” The study was published on May 20, 2016, in the journal Gut.

Related Links:
University of Leuven
Bühlmann Laboratories
Illumina