Human Milk Oligossaccharide and Acetate Production in Vivo

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance
• Intervention / Treatment: Dietary supplement: Maltodextrin; Dietary supplement: Human Milk Oligossaccharide; Dietary supplement: Human Milk Oligossaccharide and resistant starch

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 5229ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 11.43 g (3 x 3.81 g) maltodextrin the day before the clinical investigation day	Dietary supplement: Maltodextrin; The day before the CIDs, the participants receive the supplements 3x a day in randomized order
Active Comparator: Human milk-like oligosaccharide alone; 12 g (3 x 4 g) of the human milk-like oligosaccharide the day before the clinical investigation day	Dietary supplement: Human Milk Oligossaccharide; The day before the CIDs, the participants receive the supplements 3x a day in randomized order
Experimental: Human milk-like oligosaccharide and resistant starch; 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; The day before the CIDs, the participants receive the supplements 3x a day in randomized order

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): October 15, 2021
• Study Completion (Actual): October 15, 2021

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: NL71611.068.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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