Journal of Oral Microbiology (Dec 2025)

Role of immunostimulatory deoxycytidylate-phosphate-deoxyguanylate (CpG) motifs in oral bacteria associated with oral diseases

  • Pisit Charoenwongwatthana,
  • Oslovenya S. Caroline,
  • Halah Ahmed,
  • Jamie Coulter,
  • Chien-Yi Chang

DOI
https://doi.org/10.1080/20002297.2025.2486639
Journal volume & issue
Vol. 17, no. 1

Abstract

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Background CpG oligodeoxynucleotide motifs in bacterial DNA with composition variations exhibit potent immunostimulation. The effect of different compositions in oral infections is unclear. This study aims to investigate CpG motifs in bacteria associated with endodontic diseases, periodontal diseases, and dental caries to elucidate their influence on host immune response.Methods Fifty oral bacterial genomes were selected for in silico analysis to determine GC% content and CpG motif frequency in each genome. The relationships between GC% content, CpG motif frequency, and genome size were assessed using correlation analysis. Normalisation of immunostimulatory sequences was implemented to enable unbiased comparison of frequency counts among bacteria.Results Sixty percent of bacteria exhibited medium GC% content (Mdn = 44), with no significant difference among bacteria associated with these diseases (p = 0.66). A positive correlation between GC% content and CpG motif frequency, as well as genome size and CpG motifs frequency was observed. A higher-than-mean of the human immunostimulatory motif (GTCGTT, 7/14) and the mice/rabbits immunostimulatory motif (GACGTT, 9/14) was observed in core endodontic microbiota.Conclusion CpG motifs in oral bacteria might drive disease progression through host immunomodulation. Variation in bacterial CpG motifs suggests targeting these motifs offers a promising therapeutic intervention.

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