Association of FUT2 rs601338 Genotype with Colonic Mucosal Microbiome Composition, Post-Transplant Bacteremia, and All-Cause Mortality After Liver Transplantation for Primary Sclerosing Cholangitis: A Retrospective Cohort Study

作者：Ruslan A. Mammadov, Henk P. Roest, Gwenny M. Fuhler, Junhong Su, Thijmen Visseren, Janssen Hl, R Porte, Sarwa Darwish Murad, Bettina E. Hansen, Luc J. W. van der Laan, Maikel P. Peppelenbosch · 发表于：Journal of Clinical Medicine · 年份：2026 · DOI：10.3390/jcm15124755 · 研究领域：Liver Diseases and Immunity、Gallbladder and Bile Duct Disorders、Pediatric Hepatobiliary Diseases and Treatments

Background/Objectives: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently requiring liver transplantation (LTx). The gut–liver axis, host genetics, and microbial dysbiosis are thought to contribute to disease progression and post-transplant outcomes. The FUT2 rs601338 polymorphism influences mucosal fucosylation, host–microbial interactions, and susceptibility to infection. This study aimed to investigate the association between FUT2 genotype, colonic mucosal microbiome composition, post-transplant bacteremia, and all-cause mortality in a retrospective single-center PSC cohort. Methods: This retrospective cohort study included PSC patients who underwent LTx at Erasmus MC University Medical Center (Rotterdam, The Netherlands) between 1987 and 2015. Pre-transplant archival formalin-fixed paraffin-embedded (FFPE) colonic biopsy specimens were available for microbiome analysis. Of 169 transplanted patients, FFPE tissue was available for 98 individuals, and FUT2 rs601338 genotyping was successfully performed in 87 patients. Patients were classified as FUT2 non-secretors (AA, n = 28) and secretors (GA/GG, n = 59). Post-transplant bacteremia was assessed based on clinically indicated blood cultures during follow-up. Colonic mucosal microbiome composition was analyzed using 16S rRNA gene sequencing. Results: FUT2 non-secretors showed a distinct colonic mucosal microbiome profile compared with secretors, characterized by differential abundance of se...