Publisher Summary The ability to digest colostrum and milk requires specific structures and functions of the gastrointestinal tract (GIT). Colostrum composition exhibits major changes after the onset of lactation. Nutrient and non-nutrient substances can modify gastrointestinal development and function. The chapter summarizes recent data on colostrum feeding, colostrum extracts, and insulin-like growth factor-I (IGF1) on the small intestine and colon in neonatal calves during the first week of life. The small and large intestine is characterized by several layers of cells with different functions and interactions. The epithelial cell layer in the small intestine consists of a single layer of cells that lines the crypts and covers the villi. Ingestion of colostrum modifies GIT development and function, affects digestive enzyme activities and GI hormone systems, and absorptive capacity. Colostrum contains non-nutrient factors that counteract the influence of dexamethasone on the intestinal epithelial cells. Growth promoting peptides such as IGF-I retain their structure and function in the intestine because both the acid production and proteolytic activity in the neonatal abomasum are low and because factors are present in the colostrum that inhibits proteolysis.