Studying the uniqueness of the individual requires a systems approach to human biology, and contained within this systems approach is the incorporation of concepts surrounding our understanding of the interaction between microbiome and host. Harnessing of the power of the microbiome in personalized medicine has become a central focus of basic and clinical science studies. Interrogating the impact of the human gut microbiome on physiological function is a rapidly evolving field of study. It is widely accepted that a variety of host- and microbiome-associated intrinsic and extrinsic factors influence the relationship. The intestinal signaling system is highly complex and sophisticated, highlighting both how and why responses to diet and microbiome changes are unique to each individual. In animal models, researchers have made important progress in demonstrating a connection between microbiome composition and the behavioral and physiological abnormalities associated with neurodevelopmental and neurodegenerative conditions, including autistic spectrum disorders and Parkinson’s disorders and Parkinson’s disease.