The Effect of Whole Grain on Gut Microbiome and Metabolic Health

Not Applicable

• Conditions: Metabolic Disease; Injury of Gastrointestinal Tract
• Interventions: Other: Refined grain; Other: Whole grain

• Registration Number: NCT01731366
• Lead Sponsor: University of Copenhagen

Brief Summary

Objective: To identify how specific changes of the whole grain content in the diet affect the host-gut microbiome interactions with implications for metabolic health .

Design: A randomized, controlled, single-blinded, cross-over intervention trial consisting of two 8-week intervention periods, separated by a 6-week wash-out period. A total of 60 participants will be included.

Intervention: low vs. high whole grain intake.

Detailed Description

The study is designed as a randomized, controlled, single-blinded, cross-over intervention trial consisting of two 8-week interventions periods, separated by a 6-week wash-out period. A total number of 60 participants will be included. Participants consume, in randomized order, a diet rich in whole grain in the active treatment period and a refined grain diet during the control period.

Measurements: Insulin sensitivity will be assessed by means of a meal challenge test and by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) which is the primary outcome of this study. Secondary outcomes include metabolic and inflammatory markers, appetite hormones, transit time, and GM composition. Furthermore, selected control measures are included; 4-day food records and a study intervention diary.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-11-15
• Study First Submitted QC: 2012-11-20
• Study First Posted: 2012-11-21
• Primary Completion: 2014-02
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-01
• Last Update Posted: 2014-09-03
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Body mass index (BMI): 25 - 35 kg/m2
• No medical prescribed diet
• Weight stable
• No blood donation during the study
• Intense sporting activities less than 10h/ week
• Alcohol consumption less than 14 units/ week (female) and 21 units/ week (male)
• Signed written consent

Exclusion Criteria

• Pharmacological treatment; hypertension, diabetes and blood lipid regulation
• Lactating (or lactating, 6 weeks ago), pregnant (or pregnant, 3 months ago) or wish to become pregnant during the study
• Participation in another biomedical trial 1 month prior to study start
• Diagnosed with any form of diabetes, celiac disease or chronic pancreatitis
• Reported chronic gastrointestinal disorders
• Antibiotic treatment for 3 month prior to study start
• Intake of vitamin, mineral, or pre- or probiotic supplements for 1 month prior to study start
• Blood hemoglobin < 7.0 mmol/l
• Blood donation within 1 month prior to study start

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Refined grain	Refined grain	Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)
Whole grain	Whole grain	Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)

Primary Outcome Measures

Name	Time	Method
Metagenomic profile	At the end of the intervention periods	Altered quantitative metagenomics at bacterial gene- and species levels, which is a non-specific outcome, but included as the main hypothesis of the project is to test if HOMA-IR is affected via changes in the gut microbiome.
HOMA-IR	At the end of the intervention periods	Homeostasis Model Assessment of fasting Insulin Resistance (HOMA-IR: glucose (mmol/l( x insulin (pmol/l)/22.5)

Secondary Outcome Measures

Name	Time	Method
Immune markers	At the end of the intervention periods	Fasting plasma cytokines, hsCRP, and LPS/LPS-BP
Markers of one-carbon metabolism	At the end of the intervention periods	Assessed by plasma homocystein, SAM/SAH and betain
Appetite hormones	At the end of the intervention periods	Determination of different appetite hormones in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)
Body composition	At the end of the intervention periods	Measurement of body fat mass and percentage via bio-impedance
Subjective appetite sensation	At the end of the intervention periods	Assessment of subjective appetite sensation via visual analogue scales
Energy intake	At the end of the intervention periods	Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast
Colonic fermentation	At the end of the intervention periods	Measurement of breath hydrogen excretion (at before and 30, 60, 90, 120, 150, 180 after intake of standard breakfast) and plasma short-chain fatty acids (fasting and 30, 60, 120, 180 minutes after standard breakfast)
Gene expression	At the end of the intervention periods	Assessed by mRNA qPCR in whole blood and cells from whole blood stimulation. Main focus is put on genes involved in immune function and metabolic regulation.
Gastrointestinal permeability, Lactulose/ mannitol ratio	At the end of the intervention periods	5 hours urine collection following intake of lactulose and mannitol
Blood pressure	At the end of the intervention periods	Measurement of supine systolic and diastolic blood pressure (3 times)
Blood lipid profile	At the end of the interventions periods	Measurement of different blood lipids in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)
Immune cell profiling	At the end of the intervention periods	Assessed by flow cytometry of whole blood.
Markers og glucose hemostasis	At the end of the intervention periods	Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c
Mean intestinal transit time	At the end of the intervention periods	Participants are instructed in swallowing capsules containing different small non-invasive and non-absorbable plastic pellets for 6 consecutive days. On the seventh day they are having an X-ray of the abdomen taken.
Blood immune cell content	At the end of the intervention periods	Assessed by hematological cell counts
Plasma adipokines	December 2015	Leptin and adiponectin
Saliva microbial flora	At the end of the intervention periods	Determination of fasting microbial composition of flora.
Ex vivo cytokine production	At the end of the intervention periods	Production of cytokines (such as IL-1beta, IL-6) in stimulated whole blood cultures.

Trial Locations

Locations (1)

Department of Human Nutrition, University of Copenhagen; 🇩🇰 Fredriksberg, Denmark