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

Not Applicable

Completed

• Conditions: Microbiota; Metabolic Syndrome; Overweight; Digestion; Obesity; Small Intestine
• Interventions: Other: food product

• Registration Number: NCT05120661
• Lead Sponsor: Wageningen University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-10-11
• Study First Submitted QC: 2021-11-03
• Study First Posted: 2021-11-15
• Study Start: 2021-12-09
• Primary Completion: 2022-07-01
• Study Completion: 2022-07-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-26
• Last Update Posted: 2024-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Another carbohydrate-rich food product (to be determined)	food product	This is a nutritional product, such as bread or cake, containing 50 gram carbohydrates.
Carbohydrate-rich food product (to be determined)	food product	This is a nutritional product, such as bread or cake, containing 50 gram carbohydrates.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Wageningen University; 🇳🇱 Wageningen, Gelderland, Netherlands