Unraveling the influence of diseases on the metabolism of xenobiotics by the gut microbiome
The human lives in symbiosis with millions of micro-organisms. A great amount of bacteria is located in the gut of the human. These micro-organisms in combination with their unique genes are called the gastrointestinal microbiome. Only recently the role of the intestinal microbiome in the formation of metabolites of orally ingested compounds has become evident. Fundamental questions concerning the role of the gut microbiome however remain unanswered for the majority of therapeutic, toxic and diet-derived xenobiotics.
The composition of the gut microbiome is quite stable in healthy adults and contributes to the maintenance of a healthy state in adulthood. On the other hand, several pathological states are characterized by a modified composition of the intestinal microflora as already demonstrated in obesity and type 2 diabetes. Therefore, the aim of the proposed project is to develop an integrated experimental platform to identify biotransformation due to the microbiome and to evaluate the influence of different disorders (type 2 diabetes, obesity) on this 'microbiotic metabolism'. The fate of the test compounds (simvastatin, tetrabromobisphenol A and epigallocatechin gallate) in a validated in vitro gastrointestinal dialysis system with a colon phase and in well-characterized phenotypes of obese and type 2 diabetic patients, will be studied. Detection and identification of the metabolites will be achieved by advanced analytical techniques.