Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis

• Published in: Liver international Vol. 45; no. 4; pp. e16181 - n/a
• Main Authors: Özdirik, Burcin, Berger, Hilmar, Tonetti, Fernanda Raya, Cabré, Noemí, Treichel, Nicole, Clavel, Thomas, Tacke, Frank, Sigal, Michael, Schnabl, Bernd
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2025
• Subjects: Adult; Aged; Case-Control Studies; Cholangitis; Cholangitis, Sclerosing - microbiology; Cholangitis, Sclerosing - mortality; cytolysin; enterococci; Enterococcus; Enterococcus faecalis - genetics; Enterococcus faecalis - isolation & purification; Feces; Feces - chemistry; Feces - microbiology; Female; Gastrointestinal Microbiome; Gelatinase; Health risks; Hepatitis; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - microbiology; Liver; Liver Transplantation; Male; Microorganisms; Middle Aged; Mortality risk; Pathogenesis; Perforin - analysis; Perforin - genetics; primary sclerosing cholangitis; Relative abundance; RNA, Ribosomal, 16S - genetics; rRNA 16S; Survival; Therapeutic targets; Transplants & implants; Virulence; Virulence factors; Virulence Factors - genetics; gelatinase; cytolysin; primary sclerosing cholangitis; enterococci
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/liv.16181

ABSTRACT Background and Aims Primary sclerosing cholangitis (PSC) is an immune‐related cholangiopathy without treatment options beyond liver transplantation. The gut–liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol‐associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC. Methods To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects. Results High‐throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant‐free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels. Conclusion Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin‐positive E. faecalis, and to explore its role as a potential therapeutic target.