A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility

Sci Rep. 2020 Feb 20;10(1):3008. doi: 10.1038/s41598-020-59988-z.

Abstract

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acids / metabolism
  • Amino Acids / pharmacology
  • Biological Assay
  • Case-Control Studies
  • Cell Line
  • Diglycerides / metabolism
  • Diglycerides / pharmacology
  • Disease Susceptibility
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Erythritol / therapeutic use*
  • Female
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Gingiva / microbiology
  • Gingiva / pathology
  • Gingivitis / drug therapy
  • Gingivitis / metabolism*
  • Gingivitis / microbiology
  • Gingivitis / pathology
  • Hemorrhage / drug therapy
  • Hemorrhage / metabolism*
  • Hemorrhage / microbiology
  • Hemorrhage / pathology
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Metabolome*
  • Middle Aged
  • Plasmalogens / metabolism
  • Plasmalogens / pharmacology
  • Re-Epithelialization / drug effects
  • Re-Epithelialization / physiology
  • Saliva / chemistry
  • Saliva / metabolism*
  • Saliva / microbiology
  • Severity of Illness Index
  • Streptococcus mutans / growth & development
  • Streptococcus mutans / pathogenicity

Substances

  • Amino Acids
  • Diglycerides
  • Plasmalogens
  • Erythritol