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

Language
en
Document Type
Article
Issue Date
2021-09-14
First published
2021-08-17
Issue Year
2021
Authors
Denoth, Luisa
Juillerat, Pascal
Kremer, Andreas E.
Rogler, Gerhard
Scharl, Michael
Yilmaz, Bahtiyar
Bluemel, Sena
Editor
Publisher
MDPI
Abstract

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.

Journal Title
Microorganisms
Volume
9
Issue
8
Citation

Microorganisms 9.8 (2021): 1752. https://www.mdpi.com/2076-2607/9/8/1752

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