Exercise, Gastrointestinal Microbiome, Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
NAFLD, Gut microbiota, high-intensity training
Brief summary
Non-Alcoholic Fatty Liver Disease is the most common cause of chronic liver diseases. The benign non-alcoholic fatty liver, characterized by excessive fat accumulation, can evolve into non-alcoholic steatohepatitis and liver cancer. The recommendation nowadays is a lifestyle change with physical exercise and diet to reduce liver fat and improve inflammation. Besides this, a leaky gut and dysbiosis have an impact on the liver, and exercise ameliorates the diversity of gut microbiota and permeability of the intestine. The aim of this study is to find out a link between exercise and the gut-liver axis regarding the stage of liver adiposity and define exercise-responsive gut microbiome in NAFLD patients
Detailed description
For this 12-week randomised controlled intervention 60 subjects between 18 and 70 years old, diagnosed with NAFLD and body mass index under 35 kg/m2 will be recruited. They will be randomly assigned in a high-intensity aerobic interval training (n=30) and a control group with a sedentary lifestyle (n=30). The intervention group follows a supervised high-intensity aerobic interval training two times per week and additionally, an individualised home workout program to have 3 hours of aerobic training per week. Blood samples, adipose tissue biopsy, 24h-urine and faecal samples will be collected at the baseline, midway (only stool) and at the end of the study. Dietary intake will be analysed at weeks 0, 6, 12.
Interventions
BEHAVIORALhigh-intensity aerobic interval training
The intervention group will follow a high-intensity interval training protocol on a cycle ergometer for 2 times per week and 1 time an individualised home workout program to have a total exercise amount of 3 hours. Leisure time physical activity at baseline as well as during the intervention period will be assessed by Polar Active devices.
Sponsors
European Commission
Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute
Afekta
Novogene
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Clinical Microbiomics
Kuopio Research Institute of Exercise Medicine
Kuopio University Hospital
University of Eastern Finland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
The study contains two arms. One arm is the control group without any changes in their lifestyle (sedentary lifestyle) and the other arm is the intervention group with a high-intensity interval training. Both groups have no changes in their diets.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* diagnosed NAFLD * BMI:25 - 35 kg/m\^2
Exclusion criteria
* acute illness or current evidence of acute or chronic inflammatory or infective diseases * liver disease (e.g. Wilsons disease/alpha-1-antitrypsin deficiency, Hepatitis B and C, hemochromatosis) * bleeding disorder, anticoagulation medication * subjects with diagnosed type 1 diabetes or diagnosed type 2 diabetes with insulin or Glucagon-like peptide-1 agonist treatment * diagnosed depression and mental illness * any condition preventing physical activity * smokers * alcohol abuse (daily consumption ≥ 30 g for men and ≥ 20 g for women)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in liver fat content | 12 weeks (baseline and endpoint) | Changes in liver fat content by means of magnetic resonance imaging (MRI) /magnetic resonance spectroscopy (MRS) |
| Gut microbiota changes | 12 weeks (baseline and endpoint) | Changes in the composition and richness of gut microbiota through metagenomic analyses |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in low-grade inflammation | 12 weeks (baseline and endpoint) | Cytokine levels (IL1-RA, TNFα, IL-6, MCP-1, IL-1β, TGF-β, IFN-γ, IL-10) in the blood will be measured by ELISA |
| Changes in glucose profile | 14 weeks (two weeks preceding the intervention and during the last weeks of the intervention) | Using Freestyle Libre for 2 weeks before the beginning of the intervention and during the last 2 weeks of the intervention to measure tissue glucose concentrations throughout the day |
| Changes in metabolomics | 12 weeks (baseline and endpoint) | Metabolomics (small molecule intermediates and products of metabolism) in stool, blood and urine will be measured by Liquid chromatography-mass spectrometry (LC-MS) |
| The effect on body composition | 12 weeks (baseline and endpoint) | Body composition will be measured by bioimpedance |
| Changes in protein expression in adipose tissue | 12 weeks (baseline and endpoint) | To define differences in lipid and glucose metabolism related enzymes, transporters |
Countries
Finland
Outcome results
None listed