Human Milk Oligossaccharide and Acetate Production in Vivo

Study Overview
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Brief Summary
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The study investigators hypothesize (1) that the SCFA/acetate metabolism differs between metabolic phenotypes and (2) that using a mixture of fibres that differ in degree of polymerization and branching namely a resistant starch and a human-like milk oligosaccharide enhance the acetate availability in the distal colon and systemic circulation, consequently leading to its metabolic effects. To study this, the investigators will supplement lean, normoglycaemic vs. overweight/obese, prediabetic men with the fibre mixture the day before the clinical investigation day (CID) and study during the CID its effects on fasting and postprandial substrate and energy metabolism.

Official Title
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The Effects of Human-like Milk Oligosaccharide and Resistant Starch on Acetate Production and Human Substrate Metabolism

Conditions
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Obesity, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Human Milk Oligossaccharide
* Dietary Supplement: Maltodextrin
* Dietary Supplement: Human Milk Oligossaccharide and resistant starch


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Lean (BMI ≥ 20kg/m2 and ≤ 24.9kg/m2) healthy men aged 30 - 65 years as well as overweight/obese (BMI ≥ 25kg/m2 and ≤ 34.9kg/m2) prediabetic men aged between 30 - 65 years Exclusion criteria: Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.1 mmol/L and 2h glucose ≥ 11.1 mmol/L) Gastroenterological diseases or abdominal surgery; Cardiovascular diseases, cancer, liver or kidney malfunction, disease with a life expectancy shorter than 5 years; Abuse of products; alcohol and 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 3 months prior to the start of the study; Intensive exercise training more than three hours a week; Use of any medication that influences glucose or fat metabolism and inflammation (i.e. NSAIDs); Regular use of laxation products; Use of antibiotics in the last three months (antibiotics use can alter substantially the gut microbiota composition). Follow a vegan diet.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>11.43 g (3 x 3.81 g) maltodextrin the day before the clinical investigation day | Dietary Supplement: Maltodextrin<br>* The day before the CIDs, the participants receive the supplements 3x a day in randomized order<br>|
| Active Comparator: Human milk-like oligosaccharide alone<br>12 g (3 x 4 g) of the human milk-like oligosaccharide the day before the clinical investigation day | Dietary Supplement: Human Milk Oligossaccharide<br>* The day before the CIDs, the participants receive the supplements 3x a day in randomized order<br>|
| Experimental: Human milk-like oligosaccharide and resistant starch<br>12 g (3 x 4 g) of the human milk-like oligosaccharide and 7.5g resistant starch (3 x 2.5 g) the day before the clinical investigation day | Dietary Supplement: Human Milk Oligossaccharide and resistant starch<br>* The day before the CIDs, the participants receive the supplements 3x a day in randomized order<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma acetate concentrations. | During the clinical investigation day plasma acetate will be sampled | plasma acetate will be sampled during the CID before the consumption of a liquid high fat mixed meal | 
| Plasma acetate concentrations. | During the clinical investigation day plasma acetate will be sampled | plasma acetate will be sampled during the CID at t=60 minutes after consumption of a liquid high fat mixed meal | 
| Plasma acetate concentrations. | During the clinical investigation day plasma acetate will be sampled | plasma acetate will be sampled during the CID at t=120 minutes after consumption of a liquid high fat mixed meal | 
| Plasma acetate concentrations. | During the clinical investigation day plasma acetate will be sampled | plasma acetate will be sampled during the CID at t=240 minutes after consumption of a liquid high fat mixed meal | 
| Faecal acetate concentrations. | On the day of clinical investigation day, fecal acetate will be sampled | Fecal acetate will be sampled in the morning before the testday | 
| Plasma butyrate concentrations. | During the clinical investigation day, plasma butyrate will be sampled | plasma butyrate will be sampled during the CID before the consumption of a liquid high fat mixed meal | 
| Plasma butyrate concentrations. | During the clinical investigation day, plasma butyrate will be sampled | plasma butyrate will be sampled during the CID at t=60 after consumption of a liquid high fat mixed meal | 
| Plasma butyrate concentrations. | During the clinical investigation day, plasma butyrate will be sampled | plasma butyrate will be sampled during the CID at t=120 after consumption of a liquid high fat mixed meal | 
| Plasma butyrate concentrations. | During the clinical investigation day, plasma butyrate will be sampled | plasma butyrate will be sampled during the CID at t=240 minutes after consumption of a liquid high fat mixed meal | 
| Fecal butyrate concentrations. | On the day of clinical investigation day, fecal butyrate will be sampled | Fecal butyrate will be sampled in the morning before the testday | 
| Plasma propionate concentrations. | During the clinical investigation day, plasma propionate will be sampled | Plasma propionate will be sampled during the CID before the consumption of a liquid high fat mixed meal | 
| Plasma propionate concentrations. | During the clinical investigation day, plasma propionate will be sampled | Plasma propionate will be sampled during the CID t=60 minutes after the consumption of a liquid high fat mixed meal | 
| Plasma propionate concentrations. | During the clinical investigation day, plasma propionate will be sampled | Plasma propionate will be sampled during the CID t=120 minutes after the consumption of a liquid high fat mixed meal | 
| Plasma propionate concentrations. | During the clinical investigation day, plasma propionate will be sampled | Plasma propionate will be sampled during the CID t=240 minutes after the consumption of a liquid high fat mixed meal | 
| Faecal propionate concentrations. | On the day of clinical investigation day, fecal propionate will be sampled | Fecal propionate will be sampled in the morning before the testday | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy expenditure, fat and carbohydrate oxidation | Energy expenditure, fat and carbohydrate oxidation will be measured using an open-circuit ventilated hood system (Omnical, Maastricht University, The Netherlands); | Indirect calorimetry will be measured before and for 4 hours after the consumption of the liquid high-fat mixed meal during the whole CID | 
| Breath H2 using (Bedfont EC60 Gastrolyzer, Rochester, UK). | Breath H2 using (Bedfont EC60 Gastrolyzer, Rochester, UK). | Breath H2 will be sampled during the CID before and at t=30, t=60, t=90, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal | 
| Plasma glucose concentrations | Plasma glucose concentrations | Plasma glucose concentrations will be sampled during the CID before and t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal | 
| Plasma insulin concentrations | Plasma insulin concentrations | Plasma insulin concentrations will be sampled during the CID before and at t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal | 
| Plasma FFA concentrations | Plasma FFA concentrations | Plasma FFA concentrations will be sampled during the CID before and at t=0, t=30, t=60, t=120 and t=240 minutes after consumption of a liquid high fat mixed meal | 
| Faecal microbiota composition | Faecal microbiota composition will be assessed via16S rRNA gene sequencing | Faecal microbiota composition will be sampled in the morning before the testday |