Clinical trial NCT05120661: Elucidating the Role of Human Small Intestine Microbiota in Explaining Differences in Postprandial Glucose Responses
Official title: Elucidating the Role of Human Small Intestine Microbiota in Interpersonal Differences in GLYcemic Responses Upon Consumption of Food Products: A Proof of Principle Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Obesity
Overweight
Microbiota
Small Intestine
Digestion
Lead sponsor: Wageningen University
Sponsor class: OTHER
First posted: 2021-11-15
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: postprandial glucose response (iAUC) per test product
timeFrame: 0-120 minutes
measure: small intestine microbiome
timeFrame: at baseline
Secondary outcomes:
measure: macronutrients in the small intestinal aspirates
timeFrame: 0-240 minutes
measure: presence and production of (bacterial) degradation products in the small intestinal aspirates
timeFrame: 0-240 minutes
measure: digestive enzymes in the small intestinal aspirates
timeFrame: 0-240 minutes
measure: non-absorbable marker in the small intestinal aspirates
timeFrame: 0-240 minutes
measure: blood HbA1c
timeFrame: 0-240 minutes
measure: blood glucose
timeFrame: 0-240 minutes
measure: blood insulin
timeFrame: 0-240 minutes
measure: blood glucagon
timeFrame: 0-240 minutes
measure: blood total triglycerides
timeFrame: 0-240 minutes
measure: blood total free fatty acids
timeFrame: 0-240 minutes
measure: plasma gut hormones
timeFrame: 0-240 minutes
measure: breath 13C-lactosyl ureide
timeFrame: 0-240 minutes
measure: breath hydrogen
timeFrame: 0-240 minutes
measure: breath methane
timeFrame: 0-240 minutes
measure: Oral microbiome composition
timeFrame: baseline
measure: Salivary α-amylase
timeFrame: 0-240 minutes
measure: Fecal microbiota composition
timeFrame: baseline
Other outcomes:
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University
state: Gelderland
Study officials:
References: