Host - microbe interactions: new approaches to functional food development
Joseph Rafter, Department of Medical Nutrition

Summary The main goal of the project is to gather knowledge on underlying mechanisms (regulation of inflammation, homeostasis) for prevention of health problems in the modern society and to investigate how food components affect these. A major incentive is to create a sound scientific basis for development of foods that are preventive or protective especially with respect to diet and age related diseases as well as for new therapeutic approaches to diseases. Prevention must be a key issue in future health care. We plan, for the first time, to thoroughly elucidate the crosstalk between nuclear receptors (NRs) and gut flora. Identification of these pathways will open up, hitherto unsuspected, possibilities to counteract negative, disease-causing effects arising in the GI tract, through the use of synthetic/diet derived NR ligands or via modulation of the composition of the intestinal microflora (by functional foods/probiotic bacteria). Relevant diseases include e.g. inflammatory bowel diseases, cancer and obesity. Recent exciting research is indicating that gut microorganisms can regulate levels and function of NRs in the colon. We want to obtain a holistic view of the signals initiating NR activation, the activities of the NRs, the resulting regulation of gene expression and the consequences in terms of health and disease. Identified genes will be subjected to cell biological characterization followed by analysis in disease models in mice and in human biopsies. Work will initially focus on the NRs, PPAR and ER as they have been shown to be regulated by the presence of the gut flora and/or diet derived components. Identification of substances beneficial or detrimental to health is to be obtained by health profiling using chip technology (microarray mapping of expression levels). In addition, screening of the ability of substances in protection against mutations and thereby against many age-related diseases such as cancer will be setup. The rapid throughput methods will result in identification of compounds that can be further studied (e.g. in our genetically modified mouse strains), lead to novel therapeutics and can be considered for incorporation in foods. In this context, ligands to NRs, such as PPARs, are of special interest as these receptors are affected by dietary components and are connected to obesity, e.g., through regulation of adipose tissue metabolism. We also aim to develop an arsenal of health promoting food additives, composed of naturally occurring nutrients that are essential and/or beneficial for human health and that reduce the risk of diet related diseases. To obtain general usability, the additives are designed to influence the texture (e.g. as an emulsifier) of a food product, to be nutraceutical or protective and act as food preservatives (e.g., being antimicrobial and/or antioxidative), thereby enabling a reduction in consumption of currently used additives with known adverse effects. The additives are made up from conjugates between essential or health-promoting nutrients and other biomolecules. These are designed so that their natural constituents will be released upon digestion. A large number of derivatives within a related theme will be made and these will be investigated both with respect to physical properties for food incorporation and anti-microbial activity. Research towards additives that will make food products more satisfying and nutritious at an intake of a lower overall energy content will be carried out in parallel. Finally, obesity and related disorders most likely represent the next society epidemics. This project aims to identify novel approaches to prevent such disorders, through development and identification of new strategies for design of drugs and food derivatives that can, for example, improve the innate immune system in relation to chronic inflammation, be it in the skin, GI tract, genital system, lung etc. In addition to the value that our results will have for novel foods development by the food industry, discoveries made will be transferred to new biotech companies.