Proper structure and function of the gastrointestinal (GI) tract are critical for the growth and success of humans and other organisms. Disruption of the development of the GI tract as well as the developmental stage can result in altered capacity for absorption, metabolism, and excretion of nutrients, chemicals, and other xenobiotics. These effects may ultimately affect many of the body’s other organ systems.

This chapter describes the development of the human GI tract and provides a timeline of developmental processes and potential effects on toxicity. We begin with a brief review of prenatal and postnatal development of the GI tract, including structural and functional development and development of the gut microbiome, intended to provide enough background to facilitate interpretation of studies examining toxicity. We then examine how changes in the GI tract development influence toxicity, focusing on absorption and influence of the microbiome. We discuss effects of developmental stage on absorption of xenobiotics or dietary components and resulting differences in susceptibility to their effects. We describe the influence of extrinsic factors on gut development including nutrients and dietary components, pharmaceuticals, and foreign chemicals and their potential to alter normal GI tract development through direct effects, regulatory influences, or disruption of normal bacterial colonization. The influence of the gut microbiome on GI development and interactions between the microbiome and xenobiotics are rapidly growing areas of research. We expect significant growth in these areas and anticipate with excitement an increased awareness of our complex gastrointestinal system developmental process.