Project Leader
Chronic diseases are the leading causes of death and disability in Canada, and the association between chronic disease and intestinal inflammation and immunity has been well documented. Recent evidence suggests that chronic intestinal inflammation is due to a dysregulation of the gut immune system, including defects in innate immunity. Dietary nutrients play an important role in the prevention and treatment of disease by interacting directly with cells in the gut. Therefore, dietary intervention to improve gut health and immunity is a promising target for novel functional foods.
Using a porcine model of inflammation we have shown that egg- and soy-derived peptides and amino acids can modulate local intestinal immunity and reduce inflammation. Similar effects were observed using hen egg lysozyme, an antimicrobial protein involved in innate immunity, suggesting a novel nutraceutical role for lysozyme-derived peptides. We have recently identified a novel antimicrobial eggshell-associated protein, Ovocalyxin-36, however its immune-modulating activity is yet to be explored. To fully understand the nutraceutical potential of these bioactive peptides and amino acids to improve gut health and immunity, their immune-modulating and anti-inflammatory activities must be elucidated.
We propose to study the effects of novel bioactive egg- and soy-derived peptides and amino acids on the intestinal immune system and inflammatory processes, in order to improve gut health and immunity. The development of a “preventive model” based on scientific outcomes will provide effective nutritional strategies for the dietary prevention and management of chronic diseases.
Our specific objectives are:
1) To evaluate the immune-modulating and anti-inflammatory activities of bioactive peptides, and use nutrigenomic and proteomic approaches to elucidate the mechanisms by which they exert activity;
2) To characterize the role of the active peptides and amino acids in cell signaling pathways using transcriptome and bioinformatics analyses;
3) To examine interactions of bioactive peptides and amino acids with the intestinal epithelial cells and their role in maintaining gut barrier integrity;
In this study, peptides will be produced using commercially available proteases, and will be identified by HPLC and MALDI-TOF mass spectrometry. Biological activities will be characterized in vitro using cell lines, as well as ex vivo by isolating and stimulating immune cells and screening for biomarkers involved in inflammation and innate immunity, including IL-1β, IL-12, IL-6, TNF-α, IL-8, MIP-1α/β, and MCP-1. Using a mouse model, we will assess the in vivo efficacy and mechanism of action of the peptides/amino acids by analyzing local gene expression and signal transduction by real-time quantitative RT-PCR gene arrays. The induction and expansion of specific subsets of intestinal epithelial lymphocytes will be analyzed using immunofluorescence techniques. We will use a Caco-2 cell model to evaluate the effects of active peptides/amino acids on intestinal epithelial cell barrier integrity in response to inflammation or microbial challenge.
The anticipated outcomes of this project are: 1) the development of high value nutraceuticals for improving Canadian health and reducing health care expenditure; 2) transformation of Canadian agriculture to value-added products, and 3) education of highly qualified personnel (HQP) for the society.
