Inclusion Criteria:

• Male or female subject age 18-76 years.
• Diagnosis of PSC consistent with the guidelines published by the American Association for the Study of Liver Diseases (AASLD).39 All subjects must have an elevated serum ALP of at least 1.5 times upper limit of normal at baseline plus cholangiographic evidence of PSC, as demonstrated by magnetic resonance imaging, endoscopic retrograde cholangiography, or direct cholangiography, or liver biopsy.
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• Total bilirubin at screening must be ≤ 2 times upper limit of normal.
• An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and malignancy within 6 months of study entry.
• If a patient is on any of the following medications and/or supplements, he or she is expectedto remain on the same daily dose through the treatment period: UDCA, azathioprine, prednisone (or an equivalent steroid compound), methotrexate, a 5-aminosalicylic acid, biologic therapy, and/or a probiotic.
• PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease.
• Must agree to comply with the study protocol and provide informed consent.

Exclusion Criteria:

• Administration of an antibiotic within 3 months prior to the study.
• Pregnancy or attempting to become pregnant or breastfeeding.
• Presence of any of the following:
  • Hepatitis B infection;
  • Hepatitis C infection (antibody positive); patients with a history of hepatitis C infection will be eligible for this study if they have undetectable levels of HCV RNA;
  • Other cholestatic liver diseases such as primary biliary cholangitis and cholestatic diseases of pregnancy;
  • Metabolic liver diseases such as Wilson’s disease and hemochromatosis;
  • Inherited diseases of the liver such as α-1 anti trypsindeficiency;
  • Immunoglobulin G4-related cholangitis;
  • PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis (previously known as primary biliary cirrhosis);
  • Secondary sclerosing cholangitis(SSC);
  • Active acute ascending cholangitis requiringantibiotics;
  • CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile duct);
  • A liver biopsy, if one has been previously obtained, which showed non-alcoholic steatohepatitis (NASH). Patients with suspected fatty liver by imaging will not be excluded;
  • Presence of complications of advanced PSC such as hepatic encephalopathy, portal hypertension, hepato-renal syndrome and hepato-pulmonary syndrome;
  • 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;
  • Ongoing alcohol abuse (> 4 drinks per day for men, and > 2 drinks per day for women);
  • History of allergic reaction to vancomycin;
  • Moderate-to-severe renal impairment with a calculated creatinine clearance of < 60mL/min;
  • HIV/AIDS;
  • 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.