The Importance of the Gut Microbiota in Body Weight Control and Insulin Sensitivity (ANTIBIOTICS)

September 8, 2020 updated by: Maastricht University Medical Center

The Effect of the Knock Down of Gut Microbiota by Antibiotics on Parameters of Body Weight Control and Insulin Sensitivity

BACKGROUND: The relation between gut microbiota and obesity originates from animal studies, showing that the change of gut microbiota can induce changes in both insulin resistance and body composition. In addition, these studies have shown changes in gut permeability inducing a pro-inflammatory state, changes in adipose tissue function and inflammation, effects on energy harvesting and metabolism, skeletal muscle fatty acid partitioning and fat oxidation. Human data is lacking, although several studies suggested that the composition of the gut microbiota differs between lean and obese, and between diabetic and non-diabetic individuals.

OBJECTIVE: To provide insight in the physiological significance and underlying mechanisms involved in the relation between gut microbiota, energy balance and insulin sensitivity in overweight men with impaired glucose homeostasis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The view on the putative significance of gut microbiota in metabolism emerged from animal studies. Bäcked et al. showed that germ free mice had 40% less body fat compared to conventionally raised mice. Transplantation of a cecum-derived microbial community of conventional mice into germ free mice, resulted in a significant increase of body weight and insulin resistance within 2 weeks. Application of metagenomic techniques in leptin-deficient ob/ob mice showed a different proportion of bacteria belonging when compared to lean, wild-type or heterozygous mice, with a greater representation of Firmicutes and fewer Bacteroidetes. This obese gut microbiome showed an enrichment in genes involved in energy extraction from food, less energy left over in the faeces and higher contents of the short-chain fatty acids (SCFAs) propionate, acetate and butyrate in the cecum.

Furthermore, microbiota composition may alter gut permeability, and may play a role in the development of metabolic endotoxemia (inflammation) and related impairments in glucose metabolism. In addition, the gut microbiota may determine AMP-activated protein kinase (AMPK) levels in muscle and liver, thereby affecting fatty acid oxidation (substrate metabolism) and fat storage. However, underlying mechanisms are not completely understood.

Therefore, researchers within the Top Institute Food and Nutrition (TIFN) have designed a multidisciplinary project ('Microbiota, energy balance and metabolism'), to fill the unmet gap between gut microbiota and human energy metabolism. The current protocol is designed to clarify the role of the gut microbiota in host energy metabolism and insulin sensitivity, with the main focus on underlying mechanisms.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Maastricht, Netherlands
        • Maastricht University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • male
  • 35-70 years
  • caucasian
  • overweight/obese (BMI 25-35 kg/m2)
  • insulin resistant (Homeostasis Model of Assessment - Insulin Resistance (HOMA_IR) > 2.2)
  • impaired glucose tolerance (IGT: 2h plasma glucose during 75g Oral Glucose Tolerance Test(OGTT) 7.8-11.1 mmol/l) and/or impaired fasting glucose (plasma glucose ≥ 5.6 mmol/l)
  • body weight stable for at least three months (±3 kg)

Exclusion Criteria:

  • known allergic reaction to vancomycin, teicoplanin, amoxicillin and other β-lactam antibiotics (penicillins and cefalosporins) or related antibiotics
  • diabetes mellitus
  • hearing disorders
  • cardiovascular disease
  • kidney disease
  • gastrointestinal disease
  • cancer
  • asthma or bronchitis
  • liver malfunction
  • major illness with a life expectancy < 5 years
  • diseases affecting glucose tolerance (e.g. pheochromocytoma, Cushing's syndrome, acromegaly), - - use of antibiotics in the past 3 months
  • plans to lose weight and participation in organized sports activities for >3 hours per week
  • The use of β-blockers, lipid lowering-drugs, glucose-lowering agents (including all sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin), anti-oxidants or chronic corticosteroids treatment (> 7 consecutive days of treatment)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
No intervention: Placebo 3x2 capsules per day during 7 consecutive days.
Other: Placebo
Experimental: Treatment Antibiotics: Amoxicillin
Experimental: Amoxicillin (broad spectrum antibiotics) 1500 mg/day (3x2 capsules of 250 mg) during 7 consecutive days.
Drug: Amoxicillin
Experimental: Treatment Antibiotics: Vancomycin
Experimental: Vancomycin (small spectrum antibiotics) 1500mg/day (3x2 capsules of 250 mg) during 7 consecutive days
Drug: Vancomycin
Other Names:
  • Vancocin CP 250

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity
Time Frame: up to two weeks
Before and after the intervention, insulin sensitivity will be measured by using the hyperinsulinemic-euglycemic clamp technique including a glucose tracer to accurately quantify glucose fluxes at the whole body level. Glucose and Insulin levels will be determined.
up to two weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fatty Acid Handling in the muscle
Time Frame: up to two weeks
Because skeletal muscle is responsible for almost 80% of insulin-stimulated glucose disposal, and comprises up to 40% of total body mass, it can be considered to be a major tissue in the etiology of insulin resistance. Therefore, it is important to study the role of skeletal muscle substrate metabolism (fatty acid handling)in the context of this study. Fatty acids, glycerol, triacylglycerol and labelled palmitate in the chylomicron fraction will be measured.
up to two weeks
Markers of inflammation
Time Frame: up to two weeks
Low-grade inflammation seems to contribute to insulin resistance in obese insulin resistant subjects. Therefore, muscle and adipose tissue expression/secretion of inflammatory molecules (i.e. TNFα, IL-6) will be measured.
up to two weeks
Energy expenditure
Time Frame: up to two weeks
Indirect calorimetry measurements will be done to determine energy expenditure (O2 and CO2). While the gut microbiota plays an important role in nutrient metabolism and energy extraction from the diet, the determination of energy expenditure and energy content in faeces will provide important insight into the role of the gut microbiota in body weight regulation.
up to two weeks
Microbiota composition and energy content in faecal samples
Time Frame: up to two weeks
The composition of bacteria in the gut will be determined before and after intervention to link the composition to the primary and other secondary parameters. The energy content in the faeces will provide insight in the energy extraction capacity of the bacteria present.
up to two weeks
Gut wall permeability
Time Frame: up to two weeks
A proposed hypothesis is that gut permeability plays an important role in the induction of inflammation in obese insulin resistant subjects. A multi-sugar whole gut permeability assay will be performed.
up to two weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Collaborators

Top Institute Food and Nutrition

Investigators

  • Principal Investigator: Ellen E Blaak, Prof.Dr., Maastricht University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

October 22, 2012

First Submitted That Met QC Criteria

September 15, 2014

First Posted (Estimate)

September 16, 2014

Study Record Updates

Last Update Posted (Actual)

September 10, 2020

Last Update Submitted That Met QC Criteria

September 8, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-3-072

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe