Acute Microbial Switch

Sponsor

Maastricht University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05764200

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this project the investigators will test if it is possible to measure changes in intestinal gas production after supplementation of a complex fiber mixture over a 36 hour period in both lean normoglycemic individuals and individuals with insulin resistance and/or prediabetes with overweight when compared with a placebo

Changes in intestinal gas production will also be related to energy expenditure, substrate metabolism, microbial composition and related metabolites in feces, blood and urine.

Condition or Disease	Intervention/Treatment	Phase
Insulin Sensitivity Glucose Metabolism Disorders (Including Diabetes Mellitus) Hyperinsulinism	Dietary Supplement: Two day supplementation of a complex fiber mixture Dietary Supplement: Placebo supplementation	N/A

Detailed Description

In this project the investigators aim to test whether it is possible to precisely measure the changes in fermentation gas patterns after supplementation of a complex fibre mixture over a 36-hour period in both lean normoglycemic and individuals with insulin resistance and/or prediabetes with overweight when compared with a placebo. Additionally, the investigators will investigate whether changes in fermentation patterns will be directly related to changes in carbohydrate and fat oxidation and to microbial composition or related metabolites and hormones in blood, faeces, and urine.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

double-blinded

Primary Purpose:

Basic Science

Official Title:

Acute Microbial Switch Study

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Oct 31, 2025

Anticipated Study Completion Date :

Oct 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: lean normoglycaemic individuals fiber mixture Two day supplementation of 12 g (3 x 4 g) of the dietary fiber inulin in combination with 9.375 g (3 x 3.125 g (80% resistant starch (3 x 2.5 g)) granular potato starch	Dietary Supplement: Two day supplementation of a complex fiber mixture Participants will undergo a two day supplementation of a complex fiber supplement vs. placebo with a two-week washout period between the two interventions in a randomized order
Placebo Comparator: lean normoglycaemic placebo Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin	Dietary Supplement: Placebo supplementation Participants will undergo a two day supplementation of a complex fiber supplement vs. placebo with a two-week washout period between the two interventions in a randomized order
Active Comparator: overweight and/or obesity and prediabetes/insulin fiber mixture Two day supplementation of 12 g (3 x 4 g) of the dietary fiber inulin in combination with 9.375 g (3 x 3.125 g (80% resistant starch (3 x 2.5 g)) granular potato starch	Dietary Supplement: Two day supplementation of a complex fiber mixture Participants will undergo a two day supplementation of a complex fiber supplement vs. placebo with a two-week washout period between the two interventions in a randomized order
Placebo Comparator: overweight and/or obesity and prediabetes/insulin resistance placebo Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin	Dietary Supplement: Placebo supplementation Participants will undergo a two day supplementation of a complex fiber supplement vs. placebo with a two-week washout period between the two interventions in a randomized order

Outcome Measures

Primary Outcome Measures

24 hour intestinal gas concentrations [after ingestion of the supplement up until 24 hours after supplementation continuously]
changes in intestinal gas excretion (methane, hydrogen or hydrogen sulphide will be measured using gas sensors in a modified respiration chamber)

Secondary Outcome Measures

24 hour energy expenditure [after ingestion of the supplement up until 24 hours after supplementation continuously]
changes in 24 hour energy expenditure will be measured in a respiration chamber
24 hour substrate metabolism [after ingestion of the supplement up until 24 hours after supplementation continuously]
changes in 24 hour substrate metabolism will be measured in a respiration chamber (fat and carbohydrate oxidation)
fecal microbial metabolite concentrations [after ingestion of the supplement and 24 hours after supplementation]
the concentrations of fecal SCFA and BCFAs will be measured
Fecal microbiota composition [at baseline and 24 hours after supplementation]
Faecal microbiota composition will be assessed via16S rRNA gene sequencing
24 hour glucose monitoring [after ingestion of the supplement up until 24 hours after supplementation]
24 hour glucoses concentrations will be measured using a wearable monitor during each testday
circulating blood markers [after ingestion of the supplement at multiple timepoints up until 24 hours after supplementation]
plasma blood glucose, insulin, GLP-1, glucagon, PYY, triglycerides, FFA, SCFA and BCFA
Urine metabolites [at baseline up until 24 hours after supplementation]
urinary concentrations of phenolic compounds, p-cresol and nitrogen will be measured

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Lean normoglycemic individuals:
Lean (BMI ≥ 18.5 kg/m2 and ≤ 24.9 kg/m2 );
Normal fasting glucose (plasma glucose < 5.6 mmol/L) and a HOMA-IR< 2.2

Individuals with overweight/obesity and prediabetes/insulin resistance:

Overweight/obesity (BMI ≥ 28 kg/m2 and ≤ 40 kg/m2 );
insulin resistance (HOMA-IR>2.2) and/or impaired fasting glucose (IFG: plasma glucose ≥ 5.6 mmol/l)

For both subject groups:

Aged 30 - 75 years;
Normal blood pressure (systolic blood pressure 100-150mmHg, diastolic blood pressure 60-100 mmHg);
Weight stable for at least 3 months (± 2 kg)

Exclusion Criteria:

T2DM (defined as fasting plasma glucose ≥ 7.0 mmol/L)
Gastroenterological diseases
Abdominal surgery affecting the GI tract;
Cardiovascular diseases, cancer, liver or kidney malfunction, disease with a life expectancy shorter than five years;
Abuse of products;
Alcohol (> 15 standard units per week)
Drugs
Excessive nicotine use defined as >20 cigarettes per day;
Plans to lose weight or following of a hypocaloric diet
Regular supplementation of pre- or probiotic products, use of pre- or probiotics three months prior to the start of the study;
Intensive exercise training more than three hours a week;
Use of most medications that influence glucose or fat metabolism, like some lipid lowering-drugs (e.g., PPAR γ or PPARα (fibrates) agonists), glucose-lowering agents (including all sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin), inflammation (e.g., anti-inflammatory* or immunosuppressive drugs) and anti-oxidants;
Regular use of laxatives;
Use of antibiotics in the last three months (antibiotics use can alter substantially the gut microbiota composition).
Veganism
Lactose intolerance
For women: pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Human Biology, Maastricht University Medical Centre	Maastricht		Netherlands	6200MD
2	Maastricht University Medical Centre	Maastricht		Netherlands