This pilot clinical trial will evaluate the initial safety and feasibility of microbiota transplant therapy (MTT) inpatients with primary sclerosing cholangitis (PSC). This trial will inform development of future trials in treatment of PSC.

Inclusion Criteria:

• Ages 18-76
• Serum total bilirubin at screening ≤ 2x the upper limit of normal
• Absence of biliary obstruction and malignancy by ultrasound or equivalent imaging within 6 months of study entry
• Anticipated maintenance of current medication regimen through the treatment period (UDCA, azathioprine, corticosteroid, methotrexate, 5-ASA, biologic therapy and/or probiotic)
• 3-month washout period of obeticholic acid or other experimental therapies for PSC
• Stated willingness to comply with all study procedures and availability for the duration of trial to follow-up by telephone, in-person, email, and/or video visits or correspondence.
• Informed consent

Exclusion Criteria:

• Antibiotic therapy (except vancomycin) within 3 months or anticipated antibiotic use in the course of the MTT treatment
• Presence of complications of advanced PSC, such as hepatic encephalopathy, ascites, history of esophageal varices, portal hypertension, hepato-renal syndrome, portopulmonary syndrome, and hepato-pulmonary syndrome
• Evidence for viral hepatitis (history of Hepatitis C is eligible with undetectable HCV RNA); HIV/AIDS
• Metabolic or inherited liver disease (e.g., Wilson's, hemochromatosis, alpha-1-antitrypsin deficiency)
• Another disease involving bile ducts (e.g., primary biliary cholangitis, IgG4-related cholangitis, secondary sclerosing cholangitis)
• Evidence of cirrhosis on the last magnetic resonance cholangiopancreatography (within 6 months)
• Pregnancy or attempting to become pregnant or breastfeeding.
• History of liver transplantation, anticipated need for liver transplantation within 12- months from randomization, or a Model of End Stage Liver Disease (MELD) score of ≥15
• Active malignancy
• Active alcohol overuse (>4 drinks per day for men, and >2 drinks per day for women)
• Moderate-to-severe renal impairment with a calculated creatinine clearance of < 45 mL/min
• Neutropenia (an absolute neutrophil count < 0.5 x 109 cells/L)
• History of allergic reaction to vancomycin
• History of allergic reaction to amoxicillin or other beta-lactam antibiotics
• Any other conditions or abnormalities that, in the opinion of the investigator, may compromise the safety of the subject or interfere with the subject participating in or completing the study
• Total colectomy