Faecal Microbiota Transplantation in Patients With Microscopic Colitis

This will be an intervention pilot study with a 12-week and an optional 6-months follow-up period. It will be investigated if the infusion of suspended stool from healthy donors improves the symptoms of MC patients by restoring their disturbed intestinal microbiota. This procedure is known as faecal microbiota transplantation (FMT).

MC patients (n=10) will be randomised to receive FMT using stool from one of two healthy donors.

At baseline, blood samples and mucosal biopsies will be obtained from the descending colon. In addition, faecal samples will be collected and patients will complete symptom questionnaires. The first FMT will be administered by colonoscopy, FMT 2-3 by enemas. Faecal samples will be collected and questionnaires will be completed at different time points during the study. The patients will be followed-up at 6 weeks, 8 weeks, 12 weeks and 6 months after receiving FMT 1, however, the follow-up after 6 months will be optional. Additional biopsies from the descending colon and blood samples will be collected 6 weeks after the first FMT.

Inclusion criteria

for patients:

• Signed informed consent
• Active MC diagnosis, defined as >3 stools a day from which at least one should be watery
• Willingness to stop budesonide treatment during participation in the trial
• Age: 18-70 years

Exclusion criteria

for patients

• Previous complicated gastrointestinal surgery
• Malignant disease except non-melanoma skin cancer
• Dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
• C. difficile or other current gastroenteritis
• Females who are pregnant or breast-feeding
• Severe endometriosis
• Antimicrobial treatment 4 weeks prior to first screening visit
• Antimicrobial prophylaxis (eg. acne, urinary tract infection)
• Regular consumption of probiotic products 4 weeks prior to randomization
• Recently diagnosed lactose intolerance (less than 6 months prior to first screening visit)
• Recently diagnosed coeliac disease (less than 6 months prior to first screening visit)
• Regular intake of NSAIDs (non steroidal anti-inflammatory drugs)
• Abuse of alcohol or drugs
• Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial

Inclusion criteria

for donors

• Signed informed consent
• High-butyrate producing microbiota in faecal samples
• Age: 18-65 years

Exclusion criteria

for donors

• Known organic gastrointestinal disease (e.g. IBD, IBS, chronic diarrhoea or constipation)
• First degree relative with IBD
• History of or present gastrointestinal malignancy or polyposis
• Recent (gastrointestinal) infection (within last 6 months)
• History of major gastrointestinal surgery (e.g. gastric bypass)
• Eosinophilic disorders of the gastrointestinal tract
• Current communicable disease (e.g. upper respiratory tract infection)
• Malignant disease and/or patients who are receiving systemic anti-neoplastic agents
• Psychiatric diseases (e.g. dementia, depression, schizophrenia, autism, Asperger Syndrome) or other incapacity for adequate cooperation
• Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis)
• Autoimmune disease and/or patients receiving immunosuppressive medications
• Major relevant allergies (e.g. food allergy, multiple allergies)
• Chronic pain syndromes (e.g. fibromyalgia)
• Chronic fatigue syndrome
• HIV, hepatitis A, B, C or known exposure within the recent 12 months
• Obesity (BMI>30) or metabolic syndrome
• Antimicrobial treatment or prophylaxis within the last 3 months
• Other chronic use of drugs that may affect the microbiome, e.g. proton pump inhibitors
• First degree relative with cardiovascular thrombosis before 50 years of age
• Females who are pregnant or breast-feeding
• Known clinically significant abnormal laboratory values
• Participation in high-risk sexual behaviours
• Abuse of alcohol or drugs
• Tattoo or body piercing within the last 6 months
• Travelling in countries with low hygiene or high infection risk for endemic diarrhoea within the last 6 months
• Positive stool testing for C. difficile, ova and parasites (e.g. Cyclospora, Isospora, Cryptosporidium), enteric pathogens (e.g. enterohaemorrhagic E. coli, Salmonella, Shigella, Yersinia, Campylobacter, Giarda antigen, amoebas)
• Positive stool testing for multiresistant bacteria (e.g. extended-spectrum beta- lactamase (ESBL) producing organisms, multi-resistant Gram-negative bacilli (MRGN) 3 and 4, vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA))
• Calprotectin > 50 μg/g of faeces
• Positive blood testing for HIV, Hepatitis A, B, C, syphilis, Human T-lymphotropic virus (HTLV), cytomegalovirus (CMV) and Epstein Barr Virus (EBV)
• Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial