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

Introduction 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.Areas covered 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.Expert opinion 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.