Unraveling the Mechanisms Underlying Primary Sclerosing Cholangitis Through a Multidisciplinary, Integrative Research Approach

* PSC SUBJECTS: INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Stated willingness to comply with all study procedures and availability for the duration of the study 2. Male or nonpregnant female, greater than or equal to 18 years of age 3. Evidence of PSC established by biochemical testing and either MRCP or ERCP. Participant must have evidence of large duct disease on imaging. 4. Agreement to adhere to Lifestyle Considerations throughout study duration. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Pregnant or lactating women or females of child-bearing age not taking measures to prevent pregnancy during the period of study. 2. History of clinical, serologic, or histopathologic evidence supporting etiologies of chronic liver disease other than PSC 3. History of liver transplantation 4. Diagnosis consistent with secondary sclerosing cholangitis (cholelithiasis, bile duct strictures secondary to ischemia, HIV cholangiopathy, etc.). 5. Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy, etc.). 6. History of liver or bile duct lesions concerning for malignancy. 7. Ca-19-9 \>130 U/microL 8. Alpha-fetoprotein level greater than 200 ng/microL. 9. Patients with active bacterial, viral, or fungal, systemic or localized infection. 10. Unwillingness to refrain from ingesting probiotics during study. 11. History of systemic disease not related to PSC that is poorly controlled or associated with declining functional status. Examples include but are not limited to: poorly controlled diabetes mellitus, chronic renal failure with eGFR is \<60 microl/min/1.73m\^2, chronic symptomatic heart failure or severe COPD. 12. Patients with history of any gastrointestinal malignancy in the last 3 years prior to enrollment will be excluded. Patients with history of any malignancy in the last 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded. 13. History of portal vein thrombosis 14. Patients with severe allergic reactions to iodine or other contrast, which cannot be controlled by premedication with antihistamines or steroids. 15. History of gastric and/or proximal small bowel surgery including bariatric surgery such as Roux-en-Y gastric bypass 16. Contraindication to monitored anesthesia care and/or medications that are commonly used for conscious sedation during GI Endoscopy 17. Use of anti-coagulant and anti-platelet agents excluding aspirin and NSAIDs 18. Contraindications to completing MRCP or MRI 19. Absolute neutrophil count below 1000/mm\^3 20. Hemoglobin level below 10.0 g/dl 21. Platelet count lower than 50,000/mm\^3. 22. INR greater than or equal to 1.5, PTT greater thna or equal to 1.3 times control and/or any known history of disease associated with increased bleeding diathesis. 23. Inability to provide informed consent CONTROLS: INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Male or female greater than or equal to 18 years of age 2. Any individual who is either a parent, sibling or child of a PSC patient enrolled to the study, or an unrelated person who has been living with the patient for at least 3 consecutive months before study enrollment EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. History suggestive of PSC 2. History of chronic liver disease (except for steatosis) 3. Patients with history of any malignancy in the 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded. 4. History of Inflammatory Bowel Disease 5. Antibiotic use within the last 6 weeks 6. Pregnancy 7. Inability to provide informed consent