Potential of Prebiotic D-Tagatose for Prevention of Oral Disease

Abstract

Recent studies have shown phenotypic and metabolic heterogeneity in related species including <i>Streptococcus oralis</i>, a typical oral commensal bacterium, <i>Streptococcus mutans</i>, a cariogenic bacterium, and <i>Streptococcus gordonii</i>, which functions as an accessory pathogen in periodontopathic biofilm. In this study, metabolites characteristically contained in the saliva of individuals with good oral hygiene were determined, after which the effects of an identified prebiotic candidate, D-tagatose, on phenotype, gene expression, and metabolic profiles of those three key bacterial species were investigated. Examinations of the saliva metabolome of 18 systemically healthy volunteers identified salivary D-tagatose as associated with lower dental biofilm abundance in the oral cavity (Spearman's correlation coefficient; <i>r</i> = -0.603, <i>p</i> = 0.008), then the effects of D-tagatose on oral streptococci were analyzed <i>in vitro</i>. In chemically defined medium (CDM) containing D-tagatose as the sole carbohydrate source, <i>S. mutans</i> and <i>S. gordonii</i> each showed negligible biofilm formation, whereas significant biofilms were formed in cultures of <i>S. oralis</i>. Furthermore, even in the presence of glucose, <i>S. mutans</i> and <i>S. gordonii</i> showed growth suppression and decreases in the final viable cell count in a D-tagatose concentration-dependent manner. In contrast, no inhibitory effects of D-tagatose on the growth of <i>S. oralis</i> were observed. To investigate species-specific inhibition by D-tagatose, the metabolomic profiles of D-tagatose-treated <i>S. mutans</i>, <i>S. gordonii</i>, and <i>S. oralis</i> cells were examined. The intracellular amounts of pyruvate-derived amino acids in <i>S. mutans</i> and <i>S. gordonii</i>, but not in <i>S. oralis</i>, such as branched-chain amino acids and alanine, tended to decrease in the presence of D-tagatose. This phenomenon indicates that D-tagatose inhibits growth of those bacteria by affecting glycolysis and its downstream metabolism. In conclusion, the present study provides evidence that D-tagatose is abundant in saliva of individuals with good oral health. Additionally, experimental results demonstrated that D-tagatose selectively inhibits growth of the oral pathogens <i>S. mutans</i> and <i>S. gordonii</i>. In contrast, the oral commensal <i>S. oralis</i> seemed to be negligibly affected, thus highlighting the potential of administration of D-tagatose as an oral prebiotic for its ability to manipulate the metabolism of those targeted oral streptococci.