Recently, the interest on the gut microbiome as modulator of pigs’ health largely grew. An early colonization of the gastrointestinal tract by a stable microbiome positively affects the programming of the physiological development of pigs. The processes governing the settlement and the maintenance of a balanced intestinal microbiota are not fully understood, nevertheless the Special Issue will focus on the integrated system piglet-sow-post-weaning, as a target to favor the physiological development of pigs. Piglet intervention will be presented, as well a critical review on the challenge and the opportunity of the rapid progress of the analytical tools for studies on the gut microbiota structure. Journal of Animal Science and Biotechnology is a leading open access journal publishing innovative research across agriculture, dairy and animal science.