A Personal Microbiome-dependent Glucose Response in Healthy Young Volunteers

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Blood Glucose, High

Intervention / Treatment
-----------------
* Other: Standardized breakfast


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Acute meal test
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol and breakfast<br>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<br>* 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<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glucose tolerance, Gut microbiota, Microbial richness, Gastric emptying, Metabolomics