Intensified poultry production to meet global food demands has faced challenges associated with the removal of in-feed antibiotics due to concerns over antibiotics resistance. The reduction of low-dose antibiotics in feed has allowed for reemergence of intestinal diseases that diminish animal welfare and producer economics. Alternative mechanisms to preventing disease are therefore required. The objective of this dissertation was to examine factors that contribute to chicken development and health including intestinal structure and function, environment, and genetic selection. Chapter 2 investigated the host response to infection of the parasite Eimeria maxima that predisposes chickens to a bacterial infection Clostridium perfringens. Intestinal structure, function, inflammatory response, and epithelial composition was examined during a mild subclinical infection. Analysis of E. maxima and C. perfringens as individual infections revealed how each pathogen contributes to a co-infection. E. maxima caused a more severe inflammatory response, increasing pathology scores, shortening intestinal villi, and elongating crypts in the jejunum at peak infection. C. perfringens was shown to manipulate intestinal epithelial composition by influencing stem cells to differentiate into secretory goblet cells. The most deleterious effects were observed when the pathogens were introduced together, increasing pathology scores further, damaging intestinal villi, and increasing crypt depth. The introduction of C. perfringens and E. maxima also increased signaling for the production of reactive oxygen species, stimulation of tumor necrosis factor- that is involved in innate immunity, and decreased transcription of Hes1, which is involved in Notch signaling towards absorptive cell differentiation. Hes1 has previously been shown to be involved in the inflammatory response and could be an area of interest in determining new treatments to prevent or relieve the effects of E. maxima and C. perfringens. Chapter 3 applied an environmental perspective to disease prevention and examined the properties of C. perfringens that allow it to persist in the poultry house environment. Spores resist treatments used to sanitize poultry houses and litter has been shown to be a reservoir for disease, potentially increasing occurrence in certain houses. The metabolic and physiological properties of C. perfringens were utilized to separate the microbe from other poultry litter bacteria to enumerate spores within houses. A selective and differential medium combined with a heat treatment was developed to isolate C. perfringens spores from poultry litter samples. On average, houses that had histories of necrotic enteritis harbored a greater abundance of C. perfringens spores. Colonies that were isolated on the specialized medium were confirmed using PCR as C. perfringens. Lastly, Chapter 4 examined how genetic selection for multiple traits has influenced early intestinal development compared to divergently selected lines based on eight-week body weight. This study showed the morphological and gene expression differences between lines and revealed that most pathways involved in intestinal development are conserved through genetic selection. The major differences between lines were an increase in peptide transporter PepT1 on d5 and d7 in chicks selected for low eight-week body weight (LWS) compared to high weight selected (HWS) chicks and modern broiler Cobb500 chicks. In HWS chicks, the opposite mechanism was observed with an increase in expression of secretory goblet cell marker Muc2. The findings of these studies give multiple perspectives into poultry production and how major factors in management including nutrition, environment, and genetics can be used to increase efficiency while preventing disease. / Doctor of Philosophy / In poultry production, it is important to use management methods that help chickens grow efficiently while preventing illnesses. A few factors that contribute to the success of a producer include the use of nutrition to enhance intestine health and efficiency, a healthy environment in the poultry house, and using genetics to select for multiple traits to increase productivity. These factors have become even more significant after concerns of antibiotic resistance has eliminated the use of in-feed antimicrobials, allowing for reemergence of diseases that were suppressed. Therefore, the objective of this dissertation was to utilize each of these management strategies to determine how a common disease to the poultry industry affects the chicken intestine, how the environment influences the occurrence of this disease, and how genetic selection impacts the early development of chicks that may contribute to how they handle incidences of disease. Chapter 2 investigated how the bacteria Clostridium perfringens and parasite Eimeria maxima that are commonly seen together in the industry impact the intestinal function, structure, and how the chicken's immune systems respond to invasion by these pathogens. The major finds of this chapter included an increased inflammatory response after E. maxima infection that damaged intestinal structures. These pathogens also decreased the expression of a gene involved in absorptive cell formation that contributes to the inflammatory response. In Chapter 3, environment was investigated to determine if poultry houses that harbored more C. perfringens spores, which are resistant to sanitary treatments, predispose chickens to disease. On average, houses with more spores were correlated with increased disease occurrence. The method developed to determine isolate C. perfringens spores can also be used to monitor the abundance in poultry litter and used as a management tool to prevent or diagnose disease outbreaks. In Chapter 4, the influence of genetic selection on early intestinal development was studied using a modern line of broiler chicks compared to chicks selected for low or high body weights. This study gave insight into how intestinal development is mostly conserved after selecting for multiple genetic traits or a single trait (growth). The main differences were greater body weight in the modern line and high weight selected chicks compared to low weight selected chicks and an increase in gene expression of a peptide transporter in low weight chicks and a decrease in secretory cell expression in high weight chicks. These projects investigated multiple management strategies to address intestinal development and response to pathogens, disease occurrence, and genetic selection as tools to shape intestinal structure and composition.