Each year the National Pork Board identifies infectious disease prevention as a high-priority research area. The prevention and treatment of diseases common to swine operations represents a significant cost, both in terms of vaccinations, management intervention, and reduced performance. The negative economic impact of important pathogens is well documented. Potentially, the gastrointestinal tract and the host microbial populations represent a focal point defining the pigs’ resistance or susceptibility to pathogens. Therefore, this project is designed to quantify important aspects (e.g., diet complexity, growth performance, digestibility, microbial ecology, and nutrient metabolism) of the interactions between nutrition and health. It is anticipated that this project will further refine disease challenge models and will be a powerful tool to help unveil possible alternative strategies that will help mitigate the economic burden caused by PCV2 as well as other infectious agents (e.g., PRRSV, etc.).