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

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-03-14 DOI:10.1111/liv.16181

Burcin Özdirik, Hilmar Berger, Fernanda Raya Tonetti, Noemí Cabré, Nicole Treichel, Thomas Clavel, Frank Tacke, Michael Sigal, Bernd Schnabl

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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.

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.