The Saliva Metabolome in Association to Oral Health Status

Abstract

Periodontitis is one of the most prevalent oral diseases worldwide and is caused by multifactorial interactions between host and oral bacteria. Altered cellular metabolism of host and microbes releases a number of intermediary end products known as metabolites. There is an increasing interest in identifying metabolites from oral fluids such as saliva to widen the understanding of the complex pathogenesis of periodontitis. It is believed that some metabolites might serve as indicators toward early detection and screening of periodontitis and perhaps even for monitoring its prognosis in the future. Because contemporary periodontal screening methods are deficient, there is an urgent need for novel approaches in periodontal screening procedures. To this end, we associated oral parameters (clinical attachment level, periodontal probing depth, supragingival plaque, supragingival calculus, number of missing teeth, and removable denture) with a large set of salivary metabolites ( n = 284) obtained by mass spectrometry among a subsample ( n = 909) of nondiabetic participants from the Study of Health in Pomerania (SHIP-Trend-0). Linear regression analyses were performed in age-stratified groups and adjusted for potential confounders. A multifaceted image of associated metabolites ( n = 107) was revealed with considerable differences according to age groups. In the young (20 to 39 y) and middle-aged (40 to 59 y) groups, metabolites were predominantly associated with periodontal variables, whereas among the older subjects (≥60 y), tooth loss was strongly associated with metabolite levels. Metabolites associated with periodontal variables were clearly linked to tissue destruction, host defense mechanisms, and bacterial metabolism. Across all age groups, the bacterial metabolite phenylacetate was significantly associated with periodontal variables. Our results revealed alterations of the salivary metabolome in association with age and oral health status. Among our comprehensive panel of metabolites, periodontitis was significantly associated with the bacterial metabolite phenylacetate, a promising substance for further biomarker research.

The salivary microbiota in health and disease

“…The breakthrough of more advanced molecular techniques such as metagenomics, metatranscriptomics and metabolomics has enabled the possibility to add bacterial functions such as carbohydrate metabolism and proteolytic activity to their presence in microbial samples [61]. Accordingly, a few studies have described functional and metabolic characteristics of SM in oral health and disease [62,63]. Thus, future studies will have the possibility to focus on the possible impact of metabolic functions of the salivary microbiota as an etiological agent in periodontitis and dental caries.…”

Salivary Metabolomics: From Diagnostic Biomarker Discovery to Investigating Biological Function

“…Host-derived salivary metabolites include lactate, citrate, and urea. Urea has been shown to negatively correlate with salivary bacterial load as well as dental plaque as it is utilized by oral bacteria [60,95]. Previous metabolomic study of PS has been complicated by low spectral resolution or low number of donors [20,96].…”

Intraoral Microbial Metabolism and Association with Host Taste Perception

“…These included amino acid degradation by-products such as putrescine and 5-aminopentanoate and phenolic compounds such as 3-phenylpropionate and phenylacetate. Phenylacetate has been implicated as a biomarker in periodontal disease ( Liebsch et al 2019 ). This indicates the importance of ecological niche to the pathogenicity of oral bacteria.…”

“…The few high-concentration metabolites present in glandular saliva include citrate, lactate, and urea. Salivary urea is consumed by oral bacteria postsecretion, and WMS urea concentrations correlate inversely with both microbial load and plaque abundance ( Gardner et al 2019 ; Liebsch et al 2019 ). Lactate is arguably the most familiar salivary metabolite among dental professionals.…”