Abstract

BackgroundPeriodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss. Comprehensive profiling of the metabolite content of the saliva can enable the identification of novel pathways associated with periodontitis and highlight non-invasive markers to facilitate time and cost-effective screening efforts for the presence of periodontitis and the prediction of tooth loss.MethodsWe first investigated cross-sectional associations of 13 oral health variables with saliva levels of 562 metabolites, measured by untargeted mass spectrometry among a sub-sample (n = 938) of the Study of Health in Pomerania (SHIP-2) using linear regression models adjusting for common confounders. We took forward any candidate metabolite associated with at least two oral variables, to test for an association with a 5-year tooth loss over and above baseline oral health status using negative binomial regression models.ResultsWe identified 84 saliva metabolites that were associated with at least one oral variable cross-sectionally, for a subset of which we observed robust replication in an independent study. Out of 34 metabolites associated with more than two oral variables, baseline saliva levels of nine metabolites were positively associated with a 5-year tooth loss. Across all analyses, the metabolites 2-pyrrolidineacetic acid and butyrylputrescine were the most consistent candidate metabolites, likely reflecting oral dysbiosis. Other candidate metabolites likely reflected tissue destruction and cell proliferation.ConclusionsUntargeted metabolic profiling of saliva replicated metabolic signatures of periodontal status and revealed novel metabolites associated with periodontitis and future tooth loss.

Highlights

  • Periodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss

  • We considerably extend current evidence by identifying a set of metabolites, which were statistically significantly associated with a 5-year tooth loss over and above oral health status at baseline

  • We identified a distinct profile of saliva metabolites associated with tooth loss

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Summary

Introduction

Periodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss. Comprehensive profiling of the metabolite content of the saliva can enable the identification of novel pathways associated with periodontitis and highlight non-invasive markers to facilitate time and costeffective screening efforts for the presence of periodontitis and the prediction of tooth loss. Periodontitis is a silent disease without grave symptoms, and the associated socioeconomic burden is substantial [7]. Despite this burden, periodontitis remains understudied and there is a clear call for action by health authorities [8, 9]. Periodontitis is a multifactorial inflammatory disease driven by a dysbiotic microbiome, eliciting host defense mechanisms through interactions of pathogen-associated molecular patterns. The destruction of periodontal tissues is a consequence of the dysregulated immune response [12, 13]

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