biostudies-literatureIchikawa MTakeda Science FoundationJapan Agency for Medical Research and DevelopmentJapan Agency for Medical Research and Development (AMED)3261https://www.ebi.ac.uk/biostudies/studies/S-EPMC10241881biostudies-literatureUnknown14(1)Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral admiNature communicationsBacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.PMC10241881JP21ek0109416Golembo MJablonska JSuzuki TSugimoto SSberro-Livnat HTeratani TTabuchi TNavok SKonda MNakamoto NHayashi NChu PSBassan MKhabra EZak NKowalsman NMorikawa RBuchshtab NTaniki NKredo-Russo SShiota AKanai TFujimori SBen-Ishai NWeinstock EMiyamoto KMikami YKasuga RWeiner INInbar DIchikawa MNicenboim JMordoch RAoto YfalseBacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral admi2023-01-01T00:00:00Z2023 Jun2025-04-04T14:39:38.88Z2025-04-04T14:39:38.88ZS-EPMC102418813727735110.1038/s41467-023-39029-9