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Intestinal microbiota play a major role in health and probably in brain functioning.Microbiota develop and function closely to Hypthalamic-Pituitary-Adrenal (HPA) axis.Perturbations in sensitive developmental periods lead to unbalances in both systems.Unbalances are often related to non-healthy physical/psychological functioning.Manipulating intestinal microbiota is a promising avenue for optimizing development.The human body contains as many bacteria in the intestine as the total number of human body cells. These bacteria have a central position in human health and disease, and would also play a role in the regulation of emotions, behavior, and even higher cognitive functions. The Hypothalamic-Pituitary-Adrenal axis (HPA axis) is a major physiological stress system that produces cortisol. This hormone is involved in responding to environmental stress and also shapes many aspects of brain development. Both the HPA axis and the intestinal microbiota show rapid and profound developmental changes during the first years of life. Early environmental disturbances can affect the development of both systems. Early adversity, for example, is known to lead to later unbalances in both, as well as to psychopathological behavior and emotions. The goal of this theoretical review is to summarize current knowledge on the developmental crosstalk between the intestinal microbiota and the HPA axis, providing a basis for understanding the development and bidirectional communication between these two essential systems in human functioning.