Does variability in salivary protein concentrations influence oral microbial ecology and oral health?

Salivary protein interactions with oral microbes in vitro include aggregation, adherence, cell-killing, inhibition of metabolism, and nutrition. Such interactions might be expected to influence oral ecology. However, inconsistent results have been obtained from in vivo tests of the hypothesis that quantitative variation in salivary protein concentrations will affect oral disease prevalence. Results may have been influenced by choices made during study design, including saliva source, stimulation status, control for flow rate, and assay methods. Salivary protein concentrations also may be subject to circadian variation. Values for saliva collected at the same time of day tend to remain consistent within subjects, but events such as stress inflammation, infection, menstruation, or pregnancy may induce short-term changes. Long-term factors such as aging, systemic disease, or medication likewise may influence salivary protein concentrations. Such sources of variation may increase the sample size needed to find statistically significant differences. Clinical studies also must consider factors such as human population variation, strain and species differences in protein-microbe interactions, protein polymorphism, and synergistic or antagonistic interaction between proteins. Salivary proteins may form heterotypic complexes with unique effects, and different proteins may exert redundant effects. Patterns of protein-microbe interaction also may differ between oral sites. Future clinical studies must take those factors into account. Promising approaches might involve meta-analysis or multi- center studies, retrospective and prospective longitudinal designs, short- term measurement of salivary protein effects, and consideration of individual variation in multiple protein effects such as aggregation, adherence, and cell-killing.