CABALA Diet & Health Study (CABALA)

CirculAting Bile Acids as Biomarkers of Metabolic Health - Linking microbiotA, Diet and Health

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.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Other: Apple; Other: Oats; Dietary supplement: Lactobacillus reuteri NCIMB 30242; Other: Cornflakes

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julie A Lovegrove, Professor; Phone Number: 6418 0044(0)1183786418; Email: j.a.lovegrove@reading.ac.uk
• Study Contact Backup: Name: Camilla Pedersen, PhD; Phone Number: +44 (0)797 617 6090; Email: C.Pedersen@reading.ac.uk

Study Locations

• United Kingdom
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG6 6AP
      • Recruiting
      • Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading
      • Contact: Julie A Lovegrove, Professor; Phone Number: 6418 0044(0)1183786418; Email: j.a.lovegrove@reading.ac.uk
      • Contact: Camilla Pedersen, PhD; Phone Number: +44 (0)797 617 6090; Email: C.Pedersen@reading.ac.uk
      • Principal Investigator: Julie A Lovegrove, Professor
      • Sub-Investigator: Camilla Pedersen, PhD
      • Sub-Investigator: Kim Jackson, PhD
      • Sub-Investigator: Jeremy Spencer, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apple/ Polyphenol; Participants will be asked to consume 2 Renetta Canada apples (with skin) and 2 placebo capsules every day for 8 weeks.	Other: Apple; 2 Renetta Canada apples and 2 placebo capsules/ day; Other Names: Polyphenol
Experimental: Oats / Prebiotic; Participants will be asked to consume 40g jumbo rolled oats with semi-skimmed milk and 2 placebo capsules every day for 8 weeks.	Other: Oats; 40g jumbo rolled oats with semi-skimmed milk and 2 placebo capsules / day; Other Names: Prebiotic
Experimental: Lactobacillus reuteri NCIMB 30242 / Probiotic; Participants will be asked to consume 2 probiotic capsules and 40g cornflakes with semi-skimmed milk every day for 8 weeks.	Dietary supplement: Lactobacillus reuteri NCIMB 30242; 2 probiotic capsules and 40g cornflakes with semi-skimmed milk / day.; Other Names: Probiotic
Placebo Comparator: Placebo / cornflakes; Participants will be asked to consume 40g cornflakes with semi-skimmed milk and 2 placebo capsules every day for 8 weeks.	Other: Cornflakes; 40g cornflakes with semi-skimmed milk and 2 placebo capsules/ day.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating bile acids	Plasma bile acid profile	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood lipid profile	total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triacylglycerol (TAG) and non-esterified fatty acids (NEFA)	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Glucose response	Fasting and postprandial blood glucose concentrations	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Insulin response	Fasting and postprandial blood insulin concentrations	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
C-peptide	Fasting and postprandial blood C-peptide concentrations	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Inflammatory markers	Fasting blood concentrations of C-reactive protein (CRP), IL-18, IL-1β and tumour necrosis factor alpha (TNF-α)	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Gut hormones	Fasting and postprandial concentrations of peptide YY, Glucagon-Like Peptide 1, Fibroblast growth factor 19	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Metabolomics	Profile of metabolites in the blood (fasting and postprandial)	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Nitric Oxide	Fasting and postprandial concentrations of nitric oxide	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Cell-adhesion molecules	Fasting and postprandial concentrations of ICAM and VCAM	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Short-chain fatty acids	Fasting and postprandial circulating short-chain fatty acids concentrations and fecal short-chain fatty acid concentrations	Chronic and acute effects: Fasting and 6-hour postprandial response and faecal sample at both baseline and week 8
LDL receptor expression	LDL receptor expression in peripheral blood mononuclear cells	This will be measured at baseline
Genotyping of bile acid receptor gene	Genotyping of single-nucleotide polymorphisms (SNPs) in the FXR-encoding gene NR1H4	This will be measured at baseline
Platelets	Platelets will be collected for in-vitro studies	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Gut microbiota	Next-generation sequencing of gut bacteria and enumeration of selected bacteria using FISH (fecal samples)	At baseline and week 8
Bile acid excretion	Fecal bile acid concentrations	At baseline and week 8
Energy excretion	Bomb calorimetry of fecal samples	At baseline and week 8
Urine metabolites	Markers of intervention foods/ supplements in urine (24h urine collection)	At baseline and week 8
Blood pressure and heart rate	Ambulatory blood pressure and heart rate	Chronic and acute effects: Fasting and 6-hour postprandial response at both baseline and week 8
Body composition	Body composition measured using bio-impedance	At baseline and week 8

Collaborators and Investigators

• Sponsor: University of Reading
• Collaborators: University College Cork; Università degli Studi dell'Insubria; Fondazione Edmund Mach

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Anticipated): November 30, 2019
• Study Completion (Anticipated): December 23, 2019

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Cholesterol; Probiotics; Gut microbiota; Polyphenols; Lipid metabolism; Prebiotics; Bile acids; Gut bacteria
• Other Study ID Numbers: 17/47

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No