Overview
In this study the investigators aim is to explore the dynamics of (small) intestinal fructose catabolism in humans and ethanol production in relation to small intestinal signalling pathways and changes in pH, using 13C fructose isotope tracing techniques complemented with direct luminal sampling via small intestinal catheter in biopsy proven MASLD/MASH patients vs healthy (BMI<25) subjects. Additionally the investigators will repeat the experiment after four weeks of administering omeprazole at a dose of 40 mg twice daily. Omeprazole is a proton pump inhibitor, known to elevate pH from 2-6.
Description
The investigators will perform a non blinded single centre intervention study in 2x 11 participants
Participants will be either healthy volunteers with a BMI < 25 and Age 18-65 or patients with MASLD with a BMI >25, Age 18-65
The objective of the investigators is to study the fructose host/microbial kinetics in humans and to establish the role of (small) intestinal pH on fructose fermentation and endogenous ethanol production in a MASLD/MASH population versus healthy subjects
Subjects will be given omeprazole orally given twice a day 40mg for four weeks
At baseline and after four weeks of omeprazole, a fructose challenge test with labelled fructose and fomepizole and a gastroscopy will be performed, during which a nasal-intestinal catheter will be placed to allow for luminal sampling during the fructose challenge test.
Eligibility
Inclusion Criteria:
In case of the healthy subject group:
- Adult individuals, age > 18 <65 years
- Male or postmenopauzal females
- BMI <25
- Ability to give informed consent In case of the MASLD/MASH group
- Adult individuals, age > 18 <65 years
- Male or postmenopauzal females
- BMI > 25
- Biopsy proven MASLD/MASH
- Ability to give informed consent
Exclusion Criteria:
- History of sustained excess alcohol ingestion: daily consumption >30g/day (3 drinks per day) for males and >20 g/day (2 drinks per day) for females
- Patients with diabetes
- Bariatric surgery
- Other forms of liver disease (e.g. Hepatitis B,C, Wilson disease, hemochromatosis)
- Proton-pump inhibitor usage one year prior to study participation
- GLP1, SGLT2i or insulin use
- Antibiotic use for the past 3 months
- Probiotic or symbiotic usage
- Pregnant women
- Chronic illness (including a known history of heart failure, renal failure (eGFR <30 ml/min), pulmonary disease, gastrointestinal disorders, or hematologic diseases), or other inflammatory diseases
- Active infection
- Use of ascal, clopidogrel or other platelet inhibition
- Smoking
- Blood thinners
- Heart failure