Lactococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis

作者：Lore Van Espen, Maximilian Joseph Brol, Lila Close, Robert Schierwagen, Wen Gu, M. Keller, Boglárka Balogh, Anthony Fullam, Lander De Coninck, Tomohiro Nakamura, Michael Kuhn, Peer Bork, Wim Laleman, Jasmohan S. Bajaj, Mária Papp, Bernd Schnabl, Jonel Trebicka, Jelle Matthijnssens · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101622 · 被引用次数：2 · 研究领域：Bacteriophages and microbial interactions、Liver Disease and Transplantation、Viral gastroenteritis research and epidemiology

Background & Aims As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF). Methods The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters. Results Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of...