Short introduction to PhD thesis:

Influence of the gut microbiota and their metabolites on the development of type-2-diabetes

Currently, more than 8 Mio people in Germany are affected by Type 2 diabetes (T2D). The frequency of T2D is often strongly linked to obesity, which is still increasing especially in industrialized countries. The onset of T2D is a combination of genetic determinants and environmental factors such as fat enriched diet and a sedentary lifestyle. Typical indications for this disease are high blood glucose levels, insulin resistance, and an insulin secretory dysfunction. Recent studies have revealed that the gut microbiome plays an important role and is involved in the development of metabolic disorders like T2D. Additionally, in the combination with high-fat diet gut microbiota triggers development of metabolic endotoxemia that is associated with low-grade inflammation and thereby affects host lipid metabolism.
The aim of this study is to analyse effects of different anti-diabetic drugs, on the gastrointestinal tract with a focus on the structure and function of the gut microflora and their metabolites. Therefore changes in bacterial communities after drug application and their influence in T2D pathophysiology will be investigated with molecular fingerprinting. Based on these results metagenome analyses with 454-pyrosequencing will be conducted which allow the elucidation of almost the whole gut microbiome as well as the genetic potential. With fluorescence-in-situ-hybridization (FISH) in combination with confocal laser scanning microscopy (CLSM) the spatial distribution of the gut microbiome should be elucidated. In a parallel project complex metabolite profiles are generated with high resolution FT-ICR-MS analytics. Statistical analyses and mathematical modeling will enable us, to correlate the results of this study with metabolomic data as well as immunological and physiological data collected in parallel, in order to demonstrate the impact of gut bacteria and their metabolic performance on the development of T2D and its therapies.