Microbiota, energy balance and metabolism
Recent research suggests that the gastrointestinal microbiota and its products might play a role in the development of obesity and type 2 diabetes mellitus through effects on gut physiology, energy metabolism, body weight and insulin sensitivity.
The aim of this project was to fill the knowledge gap in the relation between gut microbiota, gut physiology and human energy metabolism by combining state-of-the-art, detailed human phenotyping and detailed characterisation of gut-microbiota composition and its functionality. Particular focus was on interactions between gut-derived short-chain fatty acids (SCFA), and liver, adipose tissue and skeletal-muscle metabolism.
The project used human intervention studies to elucidate the significance of the gut microbiota and its products, in particular SCFA, in body-weight control and insulin sensitivity. Approaches included:
- knockdown of gut microbiota via antibiotics
- SCFA administration at different sites of the colon
- SCFA dynamics after ingestion of 13C-inulin
- measurement of SCFA fluxes across gut and liver
- faecal transplants from lean donors in subjects with metabolic syndrome
Ex vivo and in vitro testing and gene-expression analysis were conducted, using adipose tissue and muscle biopsies from the human-intervention studies, to study in more detail the link between gut microbiota-derived products, adipose tissue and skeletal muscle metabolism. Data from the different human studies were used for computational modelling of human SCFA metabolism.
The relationship between microbiota composition at 6 years of age and weight gain was investigated via the KOALA children cohort study. Microbiota composition in the human-intervention and epidemiological studies were determined using HITChip methodology.
In 2014, most of the human studies were completed, giving unique results with respect to the metabolic impact of antibiotics, colonic SCFA administration, the dynamics of SCFA metabolism and faeces transplantation in humans, including detailed characterisation of microbiota composition and parameters of body-weight control and insulin sensitivity. A proof-of-concept dietary-intervention study was initiated after defining an ‘optimal’ gut SCFA composition for body-weight control and insulin sensitivity.
Insights generated in this project were expected to provide leads for the development of dietary strategies to prevent and treat obesity and obesity-related disorders.