The collaboration and symbiotic relationship between microbiota and humans is complex. Development of the gut microbiota in infants is a dynamic process that is dependent on maternal-fetal-neonatal determinants. Vast collaborative enterprises of cooperative, co-dependent, and competitive ecologies are enormously powerful when merged together as one discrete entity or organ. This forgotten and invisible organ has both benefits and harm in health throughout the life cycle and across the next generations for the long term. Rapid advances in microbiology, genomic research and metagenomics analysis have uncovered the microbial contribution in both the hugeness and diversity of the microbial sphere. As a result, simultaneous findings have repercussions for microbial growth and health in the neonatal period and extend into childhood and adulthood. Pioneer microbiota in and on the neonate may find 'windows of opportunity' to promote health and prevent diseases. Oral probiotics is one choice to alter and balance the gut microbiota. However, the heterogeneity of research outcomes cannot be applied routinely in premature infants.