A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers (MIGLUCOSE)

A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers: a Meal Test Study

Individuals eating identical meals present high variability in post-meal blood glucose response making comparisons challenging. This study evaluates in 40 healthy and fasted participants whether the postprandial glucose response upon a standardized breakfast is dependent on gut microbial richness. Gastric emptying rate, intestinal transit time, insulin, appetite hormones and measures of the intestinal microbiome and fermentation will also be analyzed in the context of postprandial glucose metabolism.

Study Overview

• Status: Completed
• Conditions: Blood Glucose, High
• Intervention / Treatment: Other: Standardized breakfast

Detailed Description

Elevated blood glucose levels constitute a major risk factor for pre-diabetic and diabetic patients. Postprandial glucose tests have been used for decades to monitor and compare glucose responses. Yet, individuals eating identical meals present high variability in post-meal blood glucose response making comparisons challenging. A recent landmark study showed that the inter-individual variation of postprandial glucose responses was associated with multiple person-specific factors including faecal microbiome factors. Gut microbial richness has for a long time been considered a hallmark of gut health and stability. Furthermore, microbial richness has been associated with colonic transit time, which together with the gastric emptying rate appear to be major determinants of the initial glycaemic response to carbohydrate-containing meals. Therefore, the aim of the study is to investigate whether postprandial glucose responses are associated with gut microbial richness, as well as secondary measures including gastric emptying rate, intestinal transit time and gut microbial composition and fermentation.

In an acute-meal study, 40 healthy fasted participants will consume a standardized breakfast including one tablet of paracetamol (for estimating gastric emptying rate) and 300 mL of juice.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 1958
    • Department of Nutrition, Exercise and Sports, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI < 27
• Willing to eat lentils, tomatoes, spaghetti, bread, butter, strawberry jam, and drink juice
• Known ability to tolerate paracetamol
• No current use of medication (oral contraceptive pill and mild antidepressants is allowed)
• Did not take antibiotics, diarrhoea inhibitors and laxatives in the 6 previous months
• Willing to collect and deliver a faecal sample on the intervention day
• Willing to eat corn and fill out a self-reported corn-intestinal transit time questionnaire
• Willing to consume a paracetamol tablet (500 mg paracetamol)

Exclusion Criteria:

• Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer's participation
• Pregnant or lactating women
• Suffering from irritable bowel disease (IBS), small intestine bacterial overgrowth (SIBO) or inflammatory bowel disease (IBD)
• Current chronic or infectious disease
• Current diagnosis of diabetes
• Blood donations within 3 months before participating in the current trial or participation in other scientific experiments
• Frequent intake of painkillers (paracetamol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paracetamol and breakfast; One tablet of paracetamol (500 mg) and a standardized breakfast will be consumed within 15 minutes one morning upon 10 hours of fasting	Other: Standardized breakfast; One tablet of paracetamol (500 mg) and a glass of water (150 mL) is consumed followed by a breakfast consisting of white bread, butter, jam, and juice (300 mL) and

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial plasma glucose at 60 min as a function of gut microbial richness	We test whether there is an inverse association between baseline fecal gut microbial richness and postprandial plasma glucose at 60 min after a standardised meal including 0.5 g paracetamol	60 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting (baseline) plasma glucose as a function of gut microbial diversity/richness	We test whether there is an inverse association between fasting plasma glucose and baseline fecal gut microbial richness (cross-sectionally)	0 min
Maximum plasma glucose concentration as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and maximum postprandial plasma glucose concentration [Cmax] after a standardised meal including 0.5 g paracetamol.	0, 15, 30, 60, 90 and 120 min
Postprandial plasma glucose extremes as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and the difference from the postprandial plasma glucose peak to the glucose level after 60 min or at the postprandial minimum between 30-120 min after a standardised meal including 0.5 g paracetamol.	0, 15, 30, 60, 90 and 120 min
Time to plasma glucose maximum concentration as a function of gut microbial diversity/richness	We test associations between gut microbial diversity/richness and the time to the postprandial plasma glucose maximum concentration [Cmax] after a standardised meal including 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min
Postprandial plasma glucose AUC as a function of gut microbial richness/diversity	We test associations between gut microbial diversity/richness and AUC 0-120 min for plasma glucose after a standardised meal including 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min
Postprandial glucose 0-60 min as a function of gastric emptying	We test associations between gastric emptying measured as AUC 0-60 min of postprandial paracetamol concentration profiles in blood and postprandial plasma glucose at 60 min during a standardised meal including 0.5 g paracetamol	0, 15, 30, 60 min
Gastric emptying and postprandial glucose 0-120 min	We test associations between gastric emptying measured as AUC 0-120 min of postprandial paracetamol concentration profiles in blood and postprandial plasma glucose AUC 0-120 min during a standardised meal test with intake of 0.5 g paracetamol	0, 15, 30, 60, 90 and 120 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saliva microbiome	Determination of saliva microbiome composition at baseline	0 min
Fecal microbiome	Determination of fecal microbiome composition at baseline	0 min
Urine metabolome	Urine metabolome as determined by untargeted metabolic profiling by LC-QTOF of all urine samples collected before the meal and postprandially from 0-150 min	0, 0-150 min
Fecal metabolome	Fecal metabolome as determined by untargeted metabolic profiling by LC-QTOF of ethanolic extracs from all baseline fecal samples collected before the intervention	0 min
Plasma metabolome	Plasma metabolome as determined by untargeted metabolic profiling by LC-QTOF of ethanolic extracs from all fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Glucose metabolism	Plasma glucose measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Plasma Insulin	Plasma insulin measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Plasma short-chain fatty acids	Plasma short-chain fatty acids measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Lipid metabolism	Bile acids in blood (fasting and postprandially) and in feces (baseline)	0, 15, 30, 60, 90 and 120 min
Glucagon like peptide 1 (GLP-1)	Plasma glucagon like peptide 1 (GLP-1) measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Peptide tyrosine tyrosine (PYY)	PYY measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Ghrelin	Ghrelin measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Gastric inhibitory polypeptide (GIP)	GIP measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Cholecystokinin (CCK)	CCK measured in fasting and postprandial plasma samples	0, 15, 30, 60, 90 and 120 min
Gastric emptying	Gastric emptying measured as postprandial paracetamol concentration profiles in blood	0, 15, 30, 60, 90 and 120 min
Postprandial breath exhalation	Fasting and postprandial breath hydrogen/methane exhalation	0, 60, 150 min
Feces short-chain fatty acids	Feces short-chain fatty acids measured in all fecal samples collected at baseline	0 min
Feces pH	Feces pH measured in all fecal samples collected at baseline	0 min
Feces energy	Feces energy measured in all fecal samples collected at baseline by bomb calorimetry	0 min
Stool consistency	Consistency of stool sample collected at baseline assessed by the Bristol stool scale	0 min
Intestinal transit time	Participants are instructed to observe the time it takes corn to travel through their gastrointestinal system five days prior to the intervention	Before intervention
Defecation patterns	Average number of poops per day and average stool consistency as assessed by Bristol stool scale	Before intervention
Gastrointestinal symptoms	Gastrointestinal symptoms measured on a 10 cm visual analog scale (VAS)	Before intervention

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Technical University of Denmark

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2018
• Primary Completion (Actual): December 11, 2018
• Study Completion (Actual): December 11, 2018

Study Registration Dates

• First Submitted: September 24, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): December 13, 2018
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Metabolomics; Gut microbiota; Gastric emptying; Glucose tolerance; Microbial richness
• Other Study ID Numbers: M233

Drug and device information, study documents

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