Staff PhD

A nutrigenomic approach in the elucidation of basic molecular mechanisms for the action of probiotic bacteria - An NMR-metabolomic study of biofluids and tissues.

Simon Metz Pedersen

Background

Fermented dairy products enriched with probiotic bacteria have developed into one of the most successful categories of functional foods with estimated retail sales of 1,2 billion Euro annually. This success is based on a growing body of evidence that the complex and vast microbial world inside our gastro-intestinal tract, also termed the intestinal microbiota, contributes to health and disease. Since the early 1990s, a substantial number of studies have supported the idea that our health can be affected by the daily consumption of specific bacteria that are marketed as probiotics. Recently a reduction in chronic inflammatory diseases through consumption of probiotics has been reported, e.g., irritable bowel syndrome (IBS) and other diseases that have a strong genetic background, such as inflammatory bowel diseases (IBDs) including Crohn’s disease and ulcerative colitis. These studies have positioned probiotics in the arena of evidence-based medicine and several meta-analyses (i.e. quantitative methods for combining the results of independent, published studies and synthesizing summaries and conclusions, which can be used to evaluate therapeutic effectiveness) have been reported. Hence, there is increasing interest in the basic understanding of the mechanisms that probiotic bacteria use to survive passage through the gut, to interact with the resident microbiota, and to affect the function of the host.

Although the molecular details of probiotic mechanisms still have to be discovered, several developments are in progress. Elucidation of the basic molecular mechanisms of individual probiotic bacteria must be expected to drive further innovations with immediate attention to focus on the general probiotic cultures that are targeted to large consumer groups and which will maintain or enhance general well being.

Aim

The aim of the present project is for the first time to approach the probiotic mechanisms of Lactobacillus paracasei F19, Lactobacillus rhamnosus and Bifidobacterium lactis in the host using metabonomics in tissue and biofluids from mice administered fermented milk products. This project will define a new beginning for obtaining an understanding of the potential health benefits associated with consumption of probiotic bacteria in dairy products. Establishment and documentation of potential health benefits associated with probiotic bacteria would benefit dairy industry, and the project is therefore highly relevant for the dairy industry. Moreover, the present project will contribute to build up a generic metabolomic platform, which can support future activities within this and adjacent areas together with quantitative nutritional studies of importance for an understanding of the nutritional effects of dairy products in general.

Research Outline

Metabonomics, defined as the quantitative measurement of the dynamic multi-parametric metabolic response of living systems to physiological stimuli or genetic modification. Current metabonomic practices rely on mass spectrometry (MS), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) to analyze metabolites. NMR spectroscopy holds a great potential as a multi-metabolite analytical tool, and many successful applications using the technique for metabonomic purposes have been reported on biofluids and also on tissues such as liver. Likewise, LC-MS and GC-MS, which provide higher resolution and higher sensitivity compared to NMR, are complementary techniques as multi-metabolite analytical tools with the latter enabling determination of metabolic lipid profiles. To elucidate the probiotic mechanisms in our host organism, mice will be administered fermented milk products. Subsequently, blood plasma, intestine, and urine samples are taken and analysed with regard to effect on metabolic responses using 1H-based NMR-metabolomics as well as GC-MS analyses and compared with data obtained from equal samples of mice not administered a fermented milk product. Both animals with a normal flora and gnotobiotic animals will be included, and the effect of sex will also be analysed.