Background Beginning at birth, the microbes in the gut perform essential duties related to the digestion and metabolism of food, the development and activation of the immune system, and the production of neurotransmitters that affect behavior and cognitive function. Objectives The objectives of this review are to: (a) provide a brief overview of the microbiome and the “microbiome-gut-brain axis”; (b) discuss factors known to affect the composition of the infant microbiome: mode of delivery, antibiotic exposure, and infant feeding patterns; and (c) present research priorities for nursing science, and clinical implications for infant health and neurocognitive development. Discussion The gut microbiome influences immunological, endocrine, and neural pathways and plays an important role in infant development. Several factors influence colonization of the infant gut microbiome. Different microbial colonization patterns are associated with vaginal versus surgical birth, exposure to antibiotics, and infant feeding patterns. Because of extensive physiological influence, infant microbial colonization patterns have the potential to impact physical and neurocognitive development and life course disease risk. Understanding these influences will inform newborn care and parental education.