Microorganisms have co-evolved with a variety of plants and animals, developing complex symbiotic relationships with their hosts and the environment. The diversity of symbionts acquired over time help their hosts to adapt, survive, and evolve more rapidly and efficiently, improving fitness across the lifespan. Understanding these synergistic relationships between humans and their endogenous microbiota may provide valuable information on human physiology and on potential mechanisms associated with the onset of diseases. This review summarizes current data on the composition and functionality of the predominant taxa of the healthy oral microbiome across different ages and habitats within the oral cavity, critically pointing out the inconsistency of methodologies for microbiological analysis and what still needs to be validated. We discuss how early acquisition and establishment of the oral microbiome are influenced by factors such as delivery type and feeding practices, and how adolescence marks a phase of significant shifts in the oral taxa due to hormonal and behavioral transitions. During adulthood, the healthy oral microbiome may acquire multistable signatures, shaped by genetic and environmental factors, while minor changes in core microorganisms are observed in the healthy aging populations. Overall, evidence shows that the oral microbiome is a complex ecosystem, continuously modulated by several factors, since its early acquisition through adulthood and into old age. Fluctuations do happen, but a resilient core community will persist over time in most humans to maintain homeostasis. Future challenges of microbiome research will rely on our ability to define multiple age-related healthy oral microbiomes across populations, so that oral dysbiosis can be detected and managed in advance. In this context, standardization of data acquisition and analysis, as well as improvements in multidisciplinary clinical diagnosis of oral health, must be pursued for a better comprehension of the balanced host–microbiome interaction.
