Acute Microbial Switch

Not Applicable

Recruiting

• Conditions: Insulin Sensitivity; Glucose Metabolism Disorders (Including Diabetes Mellitus); Hyperinsulinism
• Interventions: Dietary Supplement: Two day supplementation of a complex fiber mixture; Dietary Supplement: Placebo supplementation

• Registration Number: NCT05764200
• Lead Sponsor: Maastricht University Medical Center

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.

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 Timeline

• Study First Submitted: 2023-02-17
• Study First Submitted QC: 2023-03-01
• Study First Posted: 2023-03-10
• Study Start: 2024-01-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-20
• Last Update Posted: 2024-08-22
• Primary Completion: 2025-10-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
overweight and/or obesity and prediabetes/insulin fiber mixture	Two day supplementation of a complex 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
lean normoglycaemic placebo	Placebo supplementation	Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin
overweight and/or obesity and prediabetes/insulin resistance placebo	Placebo supplementation	Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin
lean normoglycaemic individuals fiber mixture	Two day supplementation of a complex 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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)
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
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
Fecal microbiota composition	at baseline and 24 hours after supplementation	Faecal microbiota composition will be assessed via16S rRNA gene sequencing
fecal microbial metabolite concentrations	after ingestion of the supplement and 24 hours after supplementation	the concentrations of fecal SCFA and BCFAs will be measured
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
Urine metabolites	at baseline up until 24 hours after supplementation	urinary concentrations of phenolic compounds, p-cresol and nitrogen will be measured

Trial Locations

Locations (2)

Maastricht University Medical Centre; 🇳🇱 Maastricht, Netherlands

Department of Human Biology, Maastricht University Medical Centre; 🇳🇱 Maastricht, Netherlands