Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis

Abstract

Background: Single-centre studies reported alterations of faecal microbiota in patients with primary sclerosing cholangitis (PSC). As regional factors may affect microbial communities, it is unclear if a microbial signature of PSC exists across different geographical regions. Aim: To identify a robust microbial signature of PSC independent of geography and environmental influences. Methods: We included 388 individuals (median age, 47 years; range, 15-78) from Germany and Norway in the study, 137 patients with PSC (n = 75 with colitis), 118 with ulcerative colitis (UC) and 133 healthy controls. Faecal microbiomes were analysed by 16S rRNA gene sequencing (V1-V2). Differences in relative abundances of single taxa were subjected to a meta-analysis. Results: In both cohorts, microbiota composition (beta-diversity) differed between PSC patients and controls (P < 0.001). Random forests classification discriminated PSC patients from controls in both geographical cohorts with an average area under the curve of 0.88. Compared to healthy controls, many new cohort-spanning alterations were identified in PSC, such as an increase of Proteobacteria and the bile-tolerant genus Parabacteroides, which were detected independent from geographical region. Associated colitis only had minor effects on microbiota composition, suggesting that PSC itself drives the faecal microbiota changes observed. Conclusion: Compared to healthy controls, numerous microbiota alterations are reproducible in PSC patients across geographical regions, clearly pointing towards a microbiota composition that is shaped by the disease itself and not by environmental factors. These reproducibly altered microbial populations might provide future insights into the pathophysiology of PSC.