Fecal Microbiota Transplantation, Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
NAFLD, Gut microbiome, Metabolomics
Brief summary
The goal of this pilot experimental medicine interventional study is to explore the degree of transferability of the gut microbiome and associated metabolomic changes in patients with non-alcoholic fatty liver disease (NAFLD) and fibrosis who receive faecal microbiota transplant (FMT). The main questions is aims to answer is: * To what extent is the gut microbiome transferable from donor to recipient in patients with NAFLD with fibrosis who receive FMT? * What are the dynamics of how the gut microbiome changes over time in these patients? * To what degree does the recipient metabolome change in association with this? Participants will receive up to three capsulised FMT preparations prepared from a donor selected rationally based upon their metabolomic characteristics. They will be asked to attend for serial clinical assessments (including FibroScan and MRE/ MRI-PDFF), and will also be asked to provide serial blood, urine and stool samples for assessment of microbiome and metabolome profiling.
Interventions
Capsulised faecal microbiota transplant prepared from rationally selected donor, based upon donor metabolomic charateristics
Sponsors
King's College London
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Human participants with NAFLD and fibrosis
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 18-75 years of age. 2. Previously-diagnosed NAFLD, with predicted fibrosis based upon non-invasive assessment with FibroScan (i.e. liver stiffness measurement (LSM) \> 8kPa). 3. Raised liver ALT (\> 30IU/l for men, \> 19IU/l for women) or AST (\> 37IU/l for men, \> 31IU/l for women) with negative non-invasive liver screen (including negative screen for viral hepatitis, autoimmune liver disease and metabolic liver disease, and normal echocardiogram within two years in the scenario where congestive hepatopathy may be considered). 4. Able to consent for themselves in English.
Exclusion criteria
1. Severe or life-threatening food allergy. 2. Pregnant or lactating women; or women trying to conceive. 3. Patients with suspected or confirmed cirrhosis (as assessed by clinical, radiological or histological criteria). 4. Use of particular medications, including: 1. Systemic antibiotics within the six weeks prior to study enrolment. 2. Immunosuppression that may influence risks related to FMT (including - but not limited to: use of corticosteroids within eight weeks of intervention; use of cytotoxic chemotherapy; use of azathioprine, tacrolimus, mycophenolate mofetil and/or immunosuppressive biologic therapy, e.g. infliximab). 3. Use of GLP-1 agonists. 5. Patients not expected to survive the duration of the study's follow-up (six months). 6. Swallowing difficulties that may preclude safe use of FMT capsules, including oral-motor dyscoordination. 7. Alcohol consumption \> 20g/ day. 8. Any active cancer (including treatment within the past six months). 9. Active infection at the point of recruitment, including COVID-19 infection. 10. Prior receipt of a liver transplant. 11. BMI \< 23 in Asian potential participants and BMI \< 25 in Caucasians. 12. Advanced chronic kidney disease (eGFR \< 30 ml/min). 13. Chronic intestinal disease, including coeliac disease, cystic fibrosis, inflammatory bowel disease, irritable bowel syndrome, and chronic diarrhoea. 14. Prior bariatric surgery. 15. Patients unable to undergo MRI scans (e.g. due to the individual having metallic implants).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in faecal microbiome composition | 24 weeks after initial FMT | Using 16S rRNA gene sequencing and shotgun metagenomic sequencing |
| Change in gut microbial metabolite composition | 24 weeks after initial FMT | Using 1H-NMR and mass spectrometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in liver fat on MRI | 16 weeks after initial FMT | Using MRI-PDFF |
| Changes in liver fat on FibroScan | 16 weeks after initial FMT | Using CAP |
| Changes in liver stiffness on MRI | 16 weeks after initial FMT | Using MRE |
| Changes in liver stiffness on FibroScan | 16 weeks after initial FMT | Using transient elastography |
| Changes in BMI | 24 weeks after initial FMT | Through combination of measurement of weight in kilogram and height in metres, reporting BMI in kg/m\^2 |
| Changes in lipid metabolism | 24 weeks after initial FMT | Serum lipid profile |
| Changes in insulin resistance | 24 weeks after initial FMT | Combining fasting glucose and insulin levels to generate HOMA-IR |
| Changes in HbA1c | 24 weeks after initial FMT | — |
Countries
United Kingdom
Outcome results
None listed