Healthy
Conditions
Keywords
Bile acids, Lipid metabolism, Cholesterol, Probiotics, Polyphenols, Prebiotics, Gut bacteria, Gut microbiota
Brief summary
During digestion of fatty foods, the liver produces a substance called bile which helps with the absorption of fat in the gut (small intestine). Some research studies have shown that friendly bacteria that live in our gut can change the makeup of bile (referred to as bile acids) leading to a lowering of blood cholesterol levels, an important risk factor for developing heart disease. This finding has been found in people who consume diets high in dietary fibers and probiotics that enhance the growth of friendly gut bacteria, and also plant rich foods high in polyphenols (such as apples). At present, very little is known about how the makeup of bile acids can regulate blood cholesterol levels and if their measurement in blood, urine or stool samples can be used as an indicator of human health. The aim of this study is to explore how consumption of foods which enhance the growth of friendly gut bacteria (such as probiotics, prebiotics, and plant rich foods high in polyphenols) can change the makeup of bile acids after 8 weeks. Changes in the bile acids measured in blood and stool samples will then be related to markers of health, such as blood cholesterol, glucose, insulin, vascular health and inflammatory markers.
Interventions
OTHERApple
2 Renetta Canada apples and 2 placebo capsules/ day
OTHEROats
40g jumbo rolled oats with semi-skimmed milk and 2 placebo capsules / day
DIETARY_SUPPLEMENTLactobacillus reuteri NCIMB 30242
2 probiotic capsules and 40g cornflakes with semi-skimmed milk / day.
OTHERCornflakes
40g cornflakes with semi-skimmed milk and 2 placebo capsules/ day.
Sponsors
University College Cork
Fondazione Edmund Mach
Università degli Studi dell'Insubria
University of Reading
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women * Aged 25-70 years * BMI: 23-32 kg/m2 * Fasting glucose \< 7 mmol/l * Total cholesterol \< 7.5 mmol/L * Triglycerides \< 2.3 mmol/L * Habitual breakfast consumers * Weight stable in the last three months
Exclusion criteria
* Smoker * Diabetes * Endocrine disease * Cardiovascular disease diagnosis * Gastrointestinal diseases * Pancreatic, hepatic or renal diseases * Medications that could influence study outcomes (e.g. lipid lowering medications, anti-depressants, anticoagulants) * Antibiotic use within the last three months * Food allergies (e.g. gluten, dairy, apples) and intolerances (e.g. lactose) * Alcohol or drug abuse (Drink more than 14 units of alcohol per week) * Anemia (men:haemoglobin\<130g/ L and women \<120 g/L * Planning or currently on a weight reducing program * Pregnancy, planned pregnancy in the next year or lactating * Irregular menstrual cycle * Planning or currently on a weight reducing program * Currently taking part or participation in other research studies within the last three months * Recent blood donation or unwilling to refrain from donating blood during the study * Regular consumption of probiotic or prebiotic food supplements or fiber based laxatives and unwilling stop consuming these for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating bile acids | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Plasma bile acid profile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose response | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial blood glucose concentrations |
| Insulin response | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial blood insulin concentrations |
| C-peptide | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial blood C-peptide concentrations |
| Inflammatory markers | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting blood concentrations of C-reactive protein (CRP), IL-18, IL-1β and tumour necrosis factor alpha (TNF-α) |
| Gut hormones | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial concentrations of peptide YY, Glucagon-Like Peptide 1, Fibroblast growth factor 19 |
| Metabolomics | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Profile of metabolites in the blood (fasting and postprandial) |
| Nitric Oxide | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial concentrations of nitric oxide |
| Cell-adhesion molecules | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Fasting and postprandial concentrations of ICAM and VCAM |
| Short-chain fatty acids | Chronic and acute effects: Fasting and 6-hour postprandial response and faecal sample at both baseline and week 8 | Fasting and postprandial circulating short-chain fatty acids concentrations and fecal short-chain fatty acid concentrations |
| Blood lipid profile | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triacylglycerol (TAG) and non-esterified fatty acids (NEFA) |
| Genotyping of bile acid receptor gene | This will be measured at baseline | Genotyping of single-nucleotide polymorphisms (SNPs) in the FXR-encoding gene NR1H4 |
| Platelets | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Platelets will be collected for in-vitro studies |
| Gut microbiota | At baseline and week 8 | Next-generation sequencing of gut bacteria and enumeration of selected bacteria using FISH (fecal samples) |
| Bile acid excretion | At baseline and week 8 | Fecal bile acid concentrations |
| Energy excretion | At baseline and week 8 | Bomb calorimetry of fecal samples |
| Urine metabolites | At baseline and week 8 | Markers of intervention foods/ supplements in urine (24h urine collection) |
| Blood pressure and heart rate | Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8 | Ambulatory blood pressure and heart rate |
| Body composition | At baseline and week 8 | Body composition measured using bio-impedance |
| LDL receptor expression | This will be measured at baseline | LDL receptor expression in peripheral blood mononuclear cells |
Countries
United Kingdom
Contacts
Primary ContactJulie A Lovegrove, Professor
Backup ContactCamilla Pedersen, PhD
Outcome results
None listed