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United States Department of Agriculture

Agricultural Research Service

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Research Project: Regulatory Mechanisms Induced by Health-Promoting Bioactive Food Components on Sex Steroid Hormone-Dependent Pathways, Cancer Cell-Stromal Cell Interactions, and the Gut Microbiome

Location: Diet, Genomics and Immunology Lab

Project Number: 8040-51530-056-00
Project Type: Appropriated

Start Date: Apr 02, 2014
End Date: Apr 01, 2019

Objective:
The overall goal of the project is to elucidate the molecular and cellular mechanisms that respond to selected food components to reduce the risk of chronic diseases such as cancer and obesity, with a focus on immune modulation in relation to obesity. A secondary aim is to further develop the utility of a porcine model to test the effect of probiotics and prebiotics on health maintenance through modulation of the gut microbiome and metabolome. Objective 1. Validate protective effects of bioactive food components such as glyceollins, indoles, and isothiocyanates on development of prostate cancer, and elucidate the regulation of sex steroid hormone-dependent pathways and cancer cell-stromal cell interactions as mechanisms of action by these bioactive food components. (NP107; C3, PS3B, C4, PS 4B) Objective 2. Study, in a swine model or other models as approriate, diet and gut microbiome interactions, focusing on the role of Lactobacillus, Bifidobacterium, and Bacteroides species, for the prevention of obesity and obesity-related metabolic syndrome. (NP107; C3, PS3B, C4, PS 4B)

Approach:
For Objective 1, a complementary cell culture and tumor xenograft model will be used to test and identify efficacies of bioactive compounds from the diet and elucidate the mechanisms of how these bioactive food components act. The research is expected to identify mechanisms where food components alter biological processes such as proliferation, apoptosis, cell cycles, intracellular cell signaling, inflammation, metastasis, and post-transcriptional message regulation from both cell culture and whole animal studies. Genes involved in pathways mediated by the sex steroid hormones estrogen and androgen, orphan receptors, and cytokine-mediated pathways will be characterized. The conditions that modulate these pathways will include the use of plants with different phytochemical composition to delineate the role of specific compounds along with related food matrix effects. For Objective 2, a juvenile porcine animal model as a surrogate model for humans will be used to validate the effect of selected prebiotics and probiotics on the modulation of the host immune and metabolic responses to an obesogenic diet. The research will use a whole nutrigenomic approach where transcriptomics, metabolomic and metagenomic changes are integrated to identify biomarkers associated with health and disease that can be used as targets for nutritional interventions. Data generated from these studies is expected to reveal mechanisms of action of prebiotic and probiotic products added to the diet.

Last Modified: 10/24/2014
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