A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation

作者：M. J. Hole, K. Jørgensen, K. Holm, P. Braadland, M. H. Meyer-Myklestad, A. Medhus, D. Reikvam, Alexander Götz, Krzysztof Grzyb, K. Boberg, T. Karlsen, M. Kummen, J. Hov · 发表于：Hepatology · 年份：2022 · DOI：10.1002/hep.32773 · 被引用次数：40 · 研究领域：Medicine

Background and Aims: Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. Approach and Results: We included 84 PSC and 51 liver transplanted PSC patients (PSC‐LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3–V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC‐LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC‐LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; QFDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no‐rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella, were associated with reduced LT‐free survival. Concomitant IBD was associated with reduced Akkermansia. Conclusions: Consistent mucosal microbiota features associated with PSC, PSC‐IBD, and disease severity, irrespective of LT status, highligh...