The Effect of Whole Grain on Gut Microbiome and Metabolic Health (3G)

Gut, Grain and Greens (3G): The Effect of Wholegrain on Gut Microbiome and Metabolic Health

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.

Study Overview

• Status: Unknown
• Conditions: Metabolic Disease; Injury of Gastrointestinal Tract
• Intervention / Treatment: Other: Refined grain; Other: Whole grain

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Fredriksberg, Denmark, 1958
    • Department of Human Nutrition, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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)	Other: 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)
Active Comparator: 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)	Other: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR	Homeostasis Model Assessment of fasting Insulin Resistance (HOMA-IR: glucose (mmol/l( x insulin (pmol/l)/22.5)	At the end of the intervention periods
Metagenomic profile	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.	At the end of the intervention periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean intestinal transit time	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.	At the end of the intervention periods
Gastrointestinal permeability, Lactulose/ mannitol ratio	5 hours urine collection following intake of lactulose and mannitol	At the end of the intervention periods
Colonic fermentation	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)	At the end of the intervention periods
Saliva microbial flora	Determination of fasting microbial composition of flora.	At the end of the intervention periods
Blood pressure	Measurement of supine systolic and diastolic blood pressure (3 times)	At the end of the intervention periods
Appetite hormones	Determination of different appetite hormones in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)	At the end of the intervention periods
Blood lipid profile	Measurement of different blood lipids in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)	At the end of the interventions periods
Body composition	Measurement of body fat mass and percentage via bio-impedance	At the end of the intervention periods
Subjective appetite sensation	Assessment of subjective appetite sensation via visual analogue scales	At the end of the intervention periods
Energy intake	Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast	At the end of the intervention periods
Ex vivo cytokine production	Production of cytokines (such as IL-1beta, IL-6) in stimulated whole blood cultures.	At the end of the intervention periods
Gene expression	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.	At the end of the intervention periods
Immune cell profiling	Assessed by flow cytometry of whole blood.	At the end of the intervention periods
Immune markers	Fasting plasma cytokines, hsCRP, and LPS/LPS-BP	At the end of the intervention periods
Blood immune cell content	Assessed by hematological cell counts	At the end of the intervention periods
Markers og glucose hemostasis	Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c	At the end of the intervention periods
Markers of one-carbon metabolism	Assessed by plasma homocystein, SAM/SAH and betain	At the end of the intervention periods
Plasma adipokines	Leptin and adiponectin	December 2015

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
4-days precoded food diary	Assessment of dietary intake via food frequency questionnaire as a measure of compliance	December 2014
n-3 fatty acid status	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.	At the end of the intervention periods
Alkyresorcinol	Measured in plasma as a marker of compliance to the whole grain intervention.	At the end of the intervention periods

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Technical University of Denmark
• Investigators: Principal Investigator: Lotte Lauritzen, Associate professor, University of Copenhagen

Publications and helpful links

General Publications

• Lind MV, Lauritzen L, Vestergaard H, Hansen T, Pedersen O, Kristensen M, Ross AB. One-carbon metabolism markers are associated with cardiometabolic risk factors. Nutr Metab Cardiovasc Dis. 2018 Apr;28(4):402-410. doi: 10.1016/j.numecd.2018.01.005. Epub 2018 Jan 31.
• Roager HM, Vogt JK, Kristensen M, Hansen LBS, Ibrugger S, Maerkedahl RB, Bahl MI, Lind MV, Nielsen RL, Frokiaer H, Gobel RJ, Landberg R, Ross AB, Brix S, Holck J, Meyer AS, Sparholt MH, Christensen AF, Carvalho V, Hartmann B, Holst JJ, Rumessen JJ, Linneberg A, Sicheritz-Ponten T, Dalgaard MD, Blennow A, Frandsen HL, Villas-Boas S, Kristiansen K, Vestergaard H, Hansen T, Ekstrom CT, Ritz C, Nielsen HB, Pedersen OB, Gupta R, Lauritzen L, Licht TR. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial. Gut. 2019 Jan;68(1):83-93. doi: 10.1136/gutjnl-2017-314786. Epub 2017 Nov 1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: November 15, 2012
• First Submitted That Met QC Criteria: November 20, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): September 3, 2014
• Last Update Submitted That Met QC Criteria: September 1, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: M206