Microbiota, energy balance and metabolism
The aim of this project is 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 will be on interactions between gut-derived short-chain fatty acids (SCFA), and liver, adipose tissue and skeletal-muscle metabolism.
The project uses 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 include:
- 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 are being 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 will be used for computational modelling of human SCFA metabolism.
The relationship between microbiota composition at 6 years of age and weight gain is being investigated via the KOALA children cohort study. Microbiota composition in the human-intervention and epidemiological studies will be 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 has been initiated after defining an ‘optimal’ gut SCFA composition for body-weight control and insulin sensitivity.
Insights generated in this project are expected to provide leads for the development of dietary strategies to prevent and treat obesity and obesity-related disorders.
|Scientific papers in peer-reviewed journals||2015 -Hepatic uptake of rectally administered butyrate prevents an increase in systemic butyrate concentrations in humans||View summary|
|Scientific papers in peer-reviewed journals||2015 - Gut colonization with methanobrevibacter smithii is associated with childhood weight development||View summary|
|Scientific papers in peer-reviewed journals||2015 - Short-chain fatty acids protect against high-fat-induced obesity via a PPARgamma-dependent switch from lipogenesis to fatty-acid oxidation||View summary|