The Oral Microbiome of Children: Development, Disease, and Implications Beyond Oral Health

Abstract

In the era of applied meta-omics and personalized medicine, the oral microbiome is a valuable asset. From biomarker discovery to being a powerful source of therapeutic targets and to presenting an opportunity for developing non-invasive approaches to health care, it has become clear that oral microbes may hold the answer for understanding disease, even beyond the oral cavity. Although our understanding of oral microbiome diversity has come a long way in the past 50 years, there are still many areas that need to be fine-tuned for better risk assessment and diagnosis, especially in early developmental stages of human life. Here, we discuss the factors that impact development of the oral microbiome and explore oral markers of disease, with a focus on the early oral cavity. Our ultimate goal is to put different experimental and methodological views into perspective for better assessment of early oral and systemic disease at an early age and discuss how oral microbiomes-at the community level-could provide improved assessment in individuals and populations at risk.

Keywords: Caries; Children; Microbial ecology; Oral microbiome.

Figure 1

Oral microbiome development, maturation, and emergence of oral disease markers. The early oral microbiome is mainly shaped by maternal stimuli including a possible signal from the maternal oral cavity (via placenta), as well as her gut, skin and vaginal microbiomes. During the first months, diet further modifies the oral microecosystem, specifically as far as oligosaccharides present in formula and breast milk and Immunoglobulin A1 from the later. These maternal and dietary stimuli give rise to the seeding oral community of infants, which include potentially cariogenic bacteria (e.g. S. mutans). Later in childhood, diet and environment determine the mature oral microbiome, which increases significantly in diversity including colonization with potentially cariogenic taxa. This stage is also critical for the emergence of oral disease, with sugar consumption and fermentation by potentially cariogenic taxa (along with an acidic pH) being the main determinants. However, the establishment of oral caries may be reversed by ureases encoded by certain commensals in plaque (e.g. Pasteurellaceae).

Figure 2

Biomarker discovery and translational preventive therapeutics in oral and systemic health. Effective risk assessment of oral disease and diagnostics precision at the individual level and specific populations at risk may be accomplished by implementing a framework that builds on four main stakes: i) High resolution tools to study the oral microbiome at the compositional and functional levels (“omic” techniques that simultaneously unravel community composition, potential and encoded functions); ii) Effective meta-omic integration modeling to extrapolate/translate the data to ecosystem (host) phenotype (Computational and statistical models to integrate various “omic” datasets and algorithms that allow risk prediction based on meta-omic integration networks); iii) Studies that not only include cross-sectional but also longitudinal data in larger cohorts (Valid biomarkers of oral disease in real time (pre and post disease) and at a global scale); and iv) Standardization of methods (Sample storage methods, standardization of phylogenetic markers and sequencing techniques, building of comprehensive oral microbe databases).