The Importance of the Gut Microbiota in Body Weight Control and Insulin Sensitivity
Condition: Obesity; Insulin Resistance
MeSH terms: Insulin Resistance; Body Weight
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Amoxicillin; Vancomycin; Placebo
Intervention type(s): Drug; Drug; Other
Other intervention name(s): Vancocin CP 250
Intervention MeSH terms: Amoxicillin; Vancomycin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Impaired glucose tolerance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Lipid metabolism; Anti Bacterial Agents; Gastro Intestinal Tract