Location: Diet, Genomics and Immunology Laboratory
Project Number: 8040-53000-021-000-D
Project Type: In-House Appropriated
Start Date: Mar 28, 2019
End Date: Mar 15, 2024
Objective:
Objective 1. Study the effect of resistant starch on the function of innate lymphoid cells, regulatory T cells, and regulatory macrophages in mucosal immunity and resistance to gastrointestinal infection. [NP107, C3, PS3B]
Objective 2. Examine the effect of cruciferous vegetables on the function of innate lymphoid cells, regulatory T cells, and regulatory macrophages in mucosal immunity and resistance to gastrointestinal infection. [NP107, C3, PS3B]
Objective 3. Define the effect of combining resistant starches with cruciferous vegetables on the function of innate lymphoid cells, regulatory T cells, and regulatory macrophages in mucosal immunity and resistance to gastrointestinal infection. [NP107, C3, PS3B]
Approach:
The mucosal immune system is the first line of defense against a wide variety of bacterial, viral, and parasitic pathogens and must also regulate intestinal homeostasis. There is substantial cross-talk between the host immune system and the microbiome that modulates development of mucosal immunity and maintenance of intestinal homeostasis. Diet can affect the microbiome and, therefore, gut mucosal immunity and intestinal homeostasis. The composition of the microbiome can be altered by consumption of resistant starches (RS) or cruciferous vegetables (CV); but how this translates to changes in gut mucosal immunity and resistance to disease is largely unexplored. The goal of this project is to define how RS and CV affect the interaction between the gut microbiome and immune cells. This will be accomplished using rodent and porcine models to study the effect of feeding type 2 or 3 RS, or CV on activation of innate lymphoid cells (ILCs), as well as the activity/polarization of tissue macrophages (M's), and induction of T regulatory (Treg) cells at homeostasis and after challenge by enteric pathogens. This work will lead to the development of new biomarkers of immune status responsive to changes in nutrition, the microbiome, and identify nutrient-immune interactions potentially beneficial to human health. The studies will use a complementary approach to take advantage of the strengths of each animal model system. Mice will be used as a lower cost, high-throughput screening tool to evaluate the effect of RS and CV rich in dietary aryl hydrocarbon receptor (AhR) ligands on the microbiome and gut immune parameters. The results from these studies will be distilled into candidate foods to test mechanism-based effects in a pig model that are likely to yield data highly relevant to humans. The proposed mouse models in this project plan will provide flexibility to evaluate several classes of dietary RS and CV at various concentrations and combinations to evaluate mucosal responses to both bacterial and parasitic worm infections. Changes in mucosal cell populations of ILCs, Tregs and regulatory Mfs and their functional expression in explanted cells in vitro will provide a context for a diet-dependent mechanism in disease resistance. The effects RS and CV on the microbiome will be evaluated and correlated with changes to mucosal immunity. Subsequent studies in pigs using diet combinations optimized in mice and the use of a more human-like food matrix in pig feeding studies will inform recommendations for dietary RS and CV compositions predictive of improved intestinal health in humans. This will include challenge studies using infections in pigs caused by zoonotic E. coli and Trichuris suis (Ts) that are comparable to E. coli and whipworm infections in mice and humans. We have previously reported on the changes in metabolome and microbiome of Ts infected pigs affording us the opportunity to test the effects of dietary interventions on important diseases affecting humans.
