Models and experimental approaches

Bruxelles Woluwe

Experimental animal models (through genetic, pharmacologic, surgical or nutritional manipulation) and a panel of biomarkers and techniques have been developed in order to assess the molecular mechanism underlying the “metabolic bridge” built by the gut microbiota between the gastro-intestinal tract and key organs involved in the control of energy metabolism (brain, liver, adipose tissues, muscle).

On one side, specific in vitro models, such as “Precision-Cut Liver Slices (PCLS)” and mouse adipose explants, have been implemented to study the contribution of tissue-fixed macrophages and other cell types in the metabolic response to nutrients, drugs and microbial compounds. We also developed intestinal organoids and use reporter cell lines and genetic deletion in cancer cell lines to investigate the presence and role of key microbial-related proteins.

On the other side, the integrative physiology of the different metabolic systems (including the microbial one) is studied through in vivo experiments in live animals, using biochemical, surgical interventions, molecular, (meta)genomic and metabolomics approaches in biological fluids and tissues.

Finally, nutritional intervention studies and cohort studies are also performed in humans, in collaboration with colleagues at the St Luc University Hospital, University Hospital Gent and University Hospital Leuven, as well as with colleagues from abroad.

A decade ago, one of our breakthroughs has been the identification of the role of the endocannabinoid system and its interaction with the gut microbiota in the development of adipose tissue and metabolic inflammation associated with obesity, insulin resistance and type 2 diabetes.

To this aim, specific animal models of tissue specific genetic deletions of genes involved in the host-bacteria interaction or in the synthesis of endocannabinoids are currently developed and studied. In addition, both in vivo and in vitro models are proposed to analyse the modulation of metabolic, oxidative, and inflammatory stresses by nutrients, ingredients and/or pharmacological compounds.