Acute Microbial Switch

Acute Microbial Switch Study

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.

Study Overview

• Status: Recruiting
• Conditions: Hyperinsulinism; Insulin Sensitivity; Glucose Metabolism Disorders (Including Diabetes Mellitus)
• Intervention / Treatment: Dietary supplement: Two day supplementation of a complex fiber mixture; Dietary supplement: Placebo supplementation

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 Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gillian Larik, Msc; Phone Number: 0433881641; Email: g.larik@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht University Medical Centre
    • Contact: Emanuel E Canfora, PhD; Phone Number: +31 43 3881 669; Email: emanuel.canfora@maastrichtuniversity.nl
  • Maastricht, Netherlands, 6200MD
    • Recruiting
    • Department of Human Biology, Maastricht University Medical Centre
    • Contact: Ellen Blaak, Prof.; Phone Number: +31(0)43-3881503; Email: e.blaak@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: insulin sensitivity; microbiota; fiber
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Insulin Resistance; Hyperinsulinism; Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: NL82078.068.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: anonymized data may be shared with other researchers for meta-analyses etc., however personalized data names etc. will not be made available

Drug and device information, study documents

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