Microorganisms (Aug 2021)

Modulation of the Mucosa-Associated Microbiome Linked to the PTPN2 Risk Gene in Patients with Primary Sclerosing Cholangitis and Ulcerative Colitis

  • Luisa Denoth,
  • Pascal Juillerat,
  • Andreas E. Kremer,
  • Gerhard Rogler,
  • Michael Scharl,
  • Bahtiyar Yilmaz,
  • Sena Bluemel,
  • on behalf of the Swiss IBD Cohort Study

DOI
https://doi.org/10.3390/microorganisms9081752
Journal volume & issue
Vol. 9, no. 8
p. 1752

Abstract

Read online

Gut microbiota appears to be involved in the pathogenesis of primary sclerosing cholangitis (PSC). The protein tyrosine phosphatase nonreceptor 2 (PTPN2) gene risk variant rs1893217 is associated with gut dysbiosis in inflammatory bowel disease (IBD), and PTPN2 was mentioned as a possible risk gene for PSC. This study assessed the microbial profile of ulcerative colitis (UC) patients with PSC and without PSC (non-PSC). Additionally, effects of the PTPN2 risk variant were assessed. In total, 216 mucosal samples from ileum, colon, and rectum were collected from 7 PSC and 42 non-PSC patients, as well as 28 control subjects (non-IBD). The microbial composition was derived from 16S rRNA sequencing data. Overall, bacterial richness was highest in PSC patients, who also had a higher relative abundance of the genus Roseburia compared to non-PSC, as well as Haemophilus, Fusobacterium, Bifidobacterium, and Actinobacillus compared to non-IBD, as well as a lower relative abundance of Bacteroides compared to non-PSC and non-IBD, respectively. After exclusion of patients with the PTPN2 risk variant, Brachyspira was higher in PSC compared to non-PSC, while, solely in colon samples, Eubacterium and Tepidimonas were higher in PSC vs. non-IBD. In conclusion, this study underlines the presence of gut mucosa-associated microbiome changes in PSC patients and rather weakens the role of PTPN2 as a PSC risk gene.

Keywords