Metabolic Disease, Injury of Gastrointestinal Tract
Conditions
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.
Interventions
OTHERWhole 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)
OTHERRefined 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)
Sponsors
Technical University of Denmark
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Saliva microbial flora | At the end of the intervention periods | Determination of fasting microbial composition of flora. |
| 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 pressure | At the end of the intervention periods | Measurement of supine systolic and diastolic blood pressure (3 times) |
| 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) |
| 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) |
| 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 |
| Gastrointestinal permeability, Lactulose/ mannitol ratio | At the end of the intervention periods | 5 hours urine collection following intake of lactulose and mannitol |
| Markers og glucose hemostasis | At the end of the intervention periods | Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c |
| Markers of one-carbon metabolism | At the end of the intervention periods | Assessed by plasma homocystein, SAM/SAH and betain |
| Plasma adipokines | December 2015 | Leptin and adiponectin |
| Energy intake | At the end of the intervention periods | Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast |
| 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. |
| 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. |
| Immune cell profiling | At the end of the intervention periods | Assessed by flow cytometry of whole blood. |
| Immune markers | At the end of the intervention periods | Fasting plasma cytokines, hsCRP, and LPS/LPS-BP |
| Blood immune cell content | At the end of the intervention periods | Assessed by hematological cell counts |
Other
| Measure | Time frame | Description |
|---|---|---|
| 4-days precoded food diary | December 2014 | Assessment of dietary intake via food frequency questionnaire as a measure of compliance |
| n-3 fatty acid status | At the end of the intervention periods | Assessed as DHA percentage in a whole blood fatty acid analysis. Included as a potential effect modificator in relation to immune function and metabolic outcomes. |
| Alkyresorcinol | At the end of the intervention periods | Measured in plasma as a marker of compliance to the whole grain intervention. |
Countries
Denmark
Outcome results
None listed