As bacteria play essential roles in maintaining human health and contributing to human illness, the establishment and maintenance of a symbiotic microbiome is key to metabolic, immunologic, and hormonal homeostasis. At no time is this more important than during infancy which is a critical period of growth and immune system development. Human milk contributes substantially to the establishment of a healthy gut microbiome in breastfed infants by providing an inoculum of >400 symbiotic and commensal bacterial species and supplying components that promote or suppress the growth of select bacteria. Yet, our mechanistic understanding of how a host responds to or modulates a bacterial challenge is deficient. This talk will focus on describing how HMOs maintain microbiome homeostasis over dysbiosis.