Oral vancomycin for primary sclerosing cholangitis and associated inflammatory bowel disease – paving a path forward

Primary sclerosing cholangitis (PSC) is a fibro-inflammatory cholangiopathy strongly associated with inflammatory bowel disease (PSC-IBD). With no approved PSC therapy, clinicians face uncertainty about oral vancomycin (OV) as a therapeutic option. This review synthesizes clinical effectiveness evidence alongside mechanistic data. We searched PubMed/Google Scholar for studies of vancomycin in PSC from 1998 through November, 2025. OV shows consistent IBD benefits and variable liver responses. In PSC-IBD, clinical and endoscopic remission occurred in 60% at 6 months and in 71% at 12 months in a pediatric cohort; in an adult single-arm study (n = 15), 80% achieved endoscopic remission at 4 weeks with universal mucosal healing, reductions in fecal calprotectin and Mayo scores, and relapse after withdrawal. For liver disease, a pediatric open-label cohort (n = 45) reported ≥50% declines in gamma-glutamyl transferase in 82%; in an adult pilot randomized controlled trial, alkaline phosphatase fell 46% at 12 weeks. Imaging/histology improved as evidenced by MRCP in 26/34 large-duct PSC and reduced portal/periportal inflammation in 11/12 small-duct PSC. No vancomycin-resistant enterococci development has been reported. OV appears effective for colitis control in PSC-IBD. Differences in observed liver outcomes across studies likely reflect variation in treatment duration, dose, and endpoint selection. Liver responses may depend on higher doses. Cross-specialty guidance and pragmatic, integrated trials are needed. Primary sclerosing cholangitis (PSC) is a long-term liver condition that is often accompanied by inflammatory bowel disease (IBD). There is no proven medical treatment for the liver disease in PSC, so doctors and patients are exploring options that might help both gut and liver. This article reviews published studies of oral vancomycin (an antibiotic taken by mouth) as a possible treatment.The medicine appears to change the mix of gut bacteria and related immune and bile acid signals that link the intestine and liver. Across case reports, observational studies, and small trials, many people with PSC-IBD experienced improved bowel symptoms on oral vancomycin. In adults, one prospective study reported that 12 of 15 patients (80%) had endoscopic remission (mucosal healing) after 4 weeks; symptoms often returned when the medicine was stopped. Liver blood tests also fell during treatment in that study. In other studies, some patients also see improvements in liver tests (for example, meaningful drops in commonly used liver markers) and reduction or resolution of itching and improvement in fatigue. Published clinical reports in PSC/PSC-IBD have not documented the emergence of vancomycin-resistant organisms. vancomycin-resistant enterococci, though careful monitoring and stewardship remain important. Responses vary, particularly in adults, and larger, coordinated studies are needed. Trials are challenging because PSC is rare and vancomycin is an older, off-patent drug. Better teamwork between liver and bowel specialists is also needed to guide care.