Acute Microbial Switch

Study Overview
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Brief Summary
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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
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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.

Official Title
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Acute Microbial Switch Study

Conditions
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Insulin Sensitivity, Hyperinsulinism, Glucose Metabolism Disorders (Including Diabetes Mellitus)

Intervention / Treatment
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* Dietary Supplement: Two day supplementation of a complex fiber mixture
* Dietary Supplement: Placebo supplementation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: lean normoglycaemic individuals fiber mixture<br>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<br>* 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<br>|
| Placebo Comparator: lean normoglycaemic placebo<br>Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin | Dietary Supplement: Placebo supplementation<br>* 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<br>|
| Active Comparator: overweight and/or obesity and prediabetes/insulin fiber mixture<br>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<br>* 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<br>|
| Placebo Comparator: overweight and/or obesity and prediabetes/insulin resistance placebo<br>Two day supplementation of 11.43 g (3 x 3.81 g) maltodextrin | Dietary Supplement: Placebo supplementation<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, insulin sensitivity, fiber