FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis

Inclusion Criteria: 1. Written informed consent 2. Age ≥ 18 years 3. Participants must be able to understand and comply with the purpose and procedures that are involved in the trial 4. An established diagnosis of colonic inflammatory bowel disease, with willingness to participate in an annual colonoscopic surveillance program, as per routine standard of care 5. An established clinical diagnosis of large duct PSC, with compatible features as assessed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) 6. A persistent ALP value above normal (at least 2 readings at this value over 6 months before screening) 7. Evidence of early to moderate stage liver fibrosis, as suspected by any of the following: 1. Median VCTE score of ≤14.4kPa, with an interquartile range ≤30% 2. Previous liver biopsy indicating at an absence of established cirrhosis, Ishak fibrosis stage \<IV (or equivalent) in the last 24 months 3. Serum enhanced liver fibrosis score (ELF) ≤9.8 8. A colonoscopy showing no evidence of dysplasia/neoplasia within 24 months before screening 9. No evidence of active colitis, as evidenced by a Partial Mayo Score of ≤4, with a score of \<2 on the rectal bleeding domain at screening 10. Individuals with IBD who are receiving treatment with biologics, immunosuppression or corticosteroids must be taking a stable dose for at least twelve weeks prior to screening, and be expected to remain on the same medication/same dose for the duration of the trial 11. Individuals with PSC having overlapping features of autoimmune hepatitis may be included, provided: 1. The dosage of immunosuppression has remained stable for at least twelve weeks prior to screening, and be expected to remain on the same medication/same dose for the duration of the trial; and 2. There is evidence of concomitant colitis Exclusion Criteria: 1. Secondary causes of sclerosing cholangitis including, but not limited to, IgG4-related cholangitis, cholangiopathy due to acquired immunodeficiency syndrome, drug-induced sclerosing cholangitis, trauma, ischaemic cholangiopathy, choledocholithiasis (investigator discretion), or sclerosing cholangiopathy as a sequelae of hepatopancreatobiliary resection 2. Other causes of liver disease, including, but not limited to, IgG4-related disease; viral hepatitis; alcohol-related liver disease; clinically significant metabolic associated fatty liver disease (at investigator discretion); drug-induced liver disease; hereditary haemochromatosis; alpha-1-antitrypsin disease; primary biliary cholangitis; Wilson disease; Budd-Chiari Syndrome; or primary or secondary hepatopancreatobiliary cancer 3. Presence of a clinically significant dominant stricture based on the combination of radiological, biochemical and clinical features. Patients can be included in the trial with a dominant extrahepatic stenosis if it has been stable for 6 months or more (as evidenced on imaging and also clinically), and one of the following are satisfied: 1. The PI does not plan for any biliary intervention (endoscopic, percutaneous or surgical) for the duration of the trial OR 2. The investigator decides that they do not wish to perform any biliary intervention (endoscopic, percutaneous or surgical) on the dominant stenosis for clinical reasons of stability/patient choice 4. Presence of a percutaneous drain or bile duct stent 5. Evidence of hepatic decompensation within twelve weeks prior to screening; or concern by the Principal Investigator that the participant may decompensate during the trial period. Hepatic decompensation as evidenced by variceal haemorrhage, ascites, hepatic hydrothorax, or hepatic encephalopathy (Appendix 1) 6. Biochemical/laboratory evidence of very advanced hepatic dysfunction, as evidenced by a serum bilirubin value \>55 µmol/L (unless Gilbert Syndrome or another condition associated with unconjugated hyperbilirubinaemia, including but not limited to, spherocytosis and disorders of bilirubin conjugation where a bilirubin value\>45 µmol/L is allowable), serum albumin \<32 g/L, platelet level of \<140x109/L, Child-Turcotte-Pugh (CTP) score \>B7, or a MELD score \>15 7. Ascending cholangitis as assessed clinically within twelve weeks of screening 8. Use of antibiotics within twelve weeks of screening 9. Participant already listed for liver transplantation, or concerns (investigator discretion) that they may need to be listed for liver transplantation during the trial period 10. Small duct PSC 11. Advanced-stage liver fibrosis, as evidenced by a VCTE score \>14.4kPa, a liver biopsy showing \>Ishak stage III fibrosis (or equivalent) 12. Significant renal dysfunction as evidenced by an estimated glomerular filtration rate of \<60 ml/min according to the Cockcroft-Gault formula, or need for dialysis 13. Human Immunodeficiency Virus (HIV) infection 14. A symptomatic positive test result for Serious Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the four weeks prior to screening 15. History of malignancy within the past three years, or ongoing malignancy, other than non-melanomatous skin cancer, or treated cervical carcinoma in situ 16. Any history of small bowel or colonic resection, or likelihood of resection during the trial period. Individuals with a sub-total colectomy and ileal pouch anal anastomosis are permitted to participate. 17. Patients who are pregnant or breastfeeding 18. Women of childbearing potential (see Appendix 2 for definition) who confirm they are not willing to practise effective contraception (see Appendix 3 for further details) for the duration of the trial and for four weeks after the last dose of trial drug. Women who are taking hormonal contraception must confirm stable formulation and dosage for at least 6 weeks prior to treatment 19. Alcohol consumption \>21 units per week for men, and \>14 units per week for women. 20. Positive urine drug screen at screening 21. Positive stool test for Clostridioides Difficile toxin or microscopy/culture positivity for enteric infection within twelve weeks prior to screening 22. Participation in an interventional trial, or use of a non-licensed investigational agent for any indication within twelve weeks before screening, or five half-lives of the investigational drug, whichever is longer 23. Newly introduced or a change in dosage of any of the following medications within twelve weeks of screening: fibric acid derivatives, farnesoid X-receptor agonists, anti-gastrointestinal motility agents (e.g., loperamide or opioids), bile acid sequestrants (e.g. colestyramine) or ursodeoxycholic acid (UDCA) 24. Use of any of the following medications within twelve weeks of screening: oral or intravenous antibiotics, including (but not limited to) vancomycin, rifaximin, rifampicin and metronidazole; probiotic or prebiotic preparations, including (but not limited to) VSL#3 and Symprove