Elucidating the Role of Human Small Intestine Microbiota in Explaining Differences in Postprandial Glucose Responses (GLYSIMI)

Elucidating the Role of Human Small Intestine Microbiota in Interpersonal Differences in GLYcemic Responses Upon Consumption of Food Products: A Proof of Principle Study

It has been shown that person-specific factors, such as the fecal microbiome, influenced postprandial glycemia. The small intestine is the site of nutrient digestion and absorption. The small intestine microbiota is amendable by dietary changes, and plays a key role in host adaptability to dietary variations. The role of the human small intestine microbiota in regulating postprandial glycemic responses towards food products will be investigated. First a screening will take place with to choose the test products that elicit most differential glucose responses and to select subjects with differential postprandial response to the same food product. The study will be a 6-day randomized cross-over trial with two test days. Four test (food) products, each containing 50 gram carbohydrates, and an oral glucose tolerance test will be provided to participants. Twenty men or women (BMI≥25 kg/m2, 40-75 years old) will be included. The main study parameters/endpoints are the food product-induced plasma glucose responses (iAUC) and the small intestine microbiota.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Metabolic Syndrome; Microbiota; Digestion; Small Intestine
• Intervention / Treatment: Other: food product

Detailed Description

Rationale: It has been shown that person-specific factors, such as the fecal microbiome, influenced postprandial glycemia. The small intestine is the site of nutrient digestion and absorption. The small intestine microbiota is amendable by dietary changes, and plays a key role in host adaptability to dietary variations. Differences in small intestine microbiota are hypothesized to be key in explaining the interpersonal differences in glycemic responses.

Objective: To investigate the role of the human small intestine microbiota in regulating postprandial glycemic responses towards food products.

Study design: The subjects will wear a continuous glucose monitor during the screening and the study. First a screening (14 days in total) will take place with to choose the test products (2 out of 4) that elicit most differential glucose responses and to select subjects with differential postprandial response to the same food product. Also an OGTT will be performed. The study will be a randomized cross-over trial with two test days (length of trial is 6 days in total). During the trial, the subjects will be intubated with a naso-jejunum catheter.

Study population: Twenty men or women (BMI≥25 kg/m2, 40-75 years old). Intervention (if applicable): Four test (food) products, each containing 50 gram carbohydrates, and an oral glucose tolerance test.

Main study parameters/endpoints: test (food) product-induced plasma glucose responses (iAUC), small intestine microbiota.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guido Hooiveld; Phone Number: +31317485788; Email: Guido.hooiveld@wur.nl
• Study Contact Backup: Name: Mara van Trijp; Phone Number: +31317 484067; Email: mara.vantrijp@wur.nl

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands
      • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males and females
• BMI≥25 kg/m2
• Age 40-75 years
• Signed informed consent

Exclusion Criteria:

• Having a history of medical or surgical events that may either put the subject at risk because of participation in the study, or influence the results of the study, including diabetes type 1, a swallowing disorder, gastrointestinal or liver disease, renal failure, cancer, nose/throat diseases, gastric bypass surgery, use of anticoagulants;
• Having a bleeding/coagulation disorder, including hemophilia, Von Willebrand disease, Bernard-Soulier, Glanzmann thrombasthenia or thrombocytopenia;
• Use of antibiotics within 2 months of starting the study or planned during the study;
• Use of medication that could influence the study results, such as diabetes treatment;
• Use of pro- and prebiotic supplements;
• Sensitive to medical skin adhesives;
• Having an allergy or intolerance towards compounds in the test products;
• Follows a vegan diet;
• Excessive alcohol consumption (on average >21 glasses/week for men and >14 glasses/week for women);
• Currently a research subject in another clinical trial;
• Having blood vessels that are too difficult for inserting a cannula/blood drawing'
• Having a hemoglobin level <8.5 mmol/l (men) or <7.5 mmol/l (women);
• Being a blood donor during the duration of the study;
• Not having a General Practitioner (GP);
• Being an employee of Wageningen University, division Human Nutrition and Health.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbohydrate-rich food product (to be determined); This is a nutritional product, such as bread or cake, containing 50 gram carbohydrates.	Other: food product; a food product containing 50 gram carbohydrates
Experimental: Another carbohydrate-rich food product (to be determined); This is a nutritional product, such as bread or cake, containing 50 gram carbohydrates.	Other: food product; a food product containing 50 gram carbohydrates

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postprandial glucose response (iAUC) per test product	iAUC glucose	0-120 minutes
small intestine microbiome	the relative composition (%) and the functional capacity (%) of the small intestine microbiota	at baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
macronutrients in the small intestinal aspirates	amounts of carbohydrates, proteins, fats	0-240 minutes
presence and production of (bacterial) degradation products in the small intestinal aspirates	concentrations of organic acids and short-chain fatty acids	0-240 minutes
digestive enzymes in the small intestinal aspirates	concentrations of amylase	0-240 minutes
non-absorbable marker in the small intestinal aspirates	peg-4000 concentrations	0-240 minutes
blood HbA1c	concentrations of HbA1c	0-240 minutes
blood glucose	concentrations glucose (e.g. GLP-1, PYY)	0-240 minutes
blood insulin	concentrations of insulin	0-240 minutes
blood glucagon	concentrations of glucagon	0-240 minutes
blood total triglycerides	concentrations of triglycerides	0-240 minutes
blood total free fatty acids	concentrations of free fatty acids	0-240 minutes
plasma gut hormones	concentrations of gut hormones (e.g. GLP-1, PYY)	0-240 minutes
breath 13C-lactosyl ureide	concentrations of 13C-lactosyl ureide	0-240 minutes
breath hydrogen	concentrations of hydrogen (ppm)	0-240 minutes
breath methane	concentrations of methane (ppm)	0-240 minutes
Oral microbiome composition	microbiota relative composition (%)	baseline
Salivary α-amylase	concentrations of a-amylase	0-240 minutes
Fecal microbiota composition	microbiota relative composition (%)	baseline

Collaborators and Investigators

• Sponsor: Wageningen University

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Overweight
• Other Study ID Numbers: NL78737.091.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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