Functional signatures of ex-vivo dental caries onset

Dina G Moussa; Ashok K Sharma; Tamer A Mansour; Bruce Witthuhn; Jorge Perdigão; Joel D Rudney; Conrado Aparicio; Andres Gomez

doi:10.1080/20002297.2022.2123624

Functional signatures of ex-vivo dental caries onset

J Oral Microbiol. 2022 Sep 19;14(1):2123624. doi: 10.1080/20002297.2022.2123624. eCollection 2022.

Authors

Dina G Moussa^{1

2}, Ashok K Sharma², Tamer A Mansour^{3

4}, Bruce Witthuhn⁵, Jorge Perdigão⁶, Joel D Rudney⁷, Conrado Aparicio^{1

6}, Andres Gomez²

Affiliations

¹ Minnesota Dental Research Center for Biomaterials and Biomechanics, Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.
² Department of Animal Science, College of Food, Agriculture and Natural Resource Sciences, University of Minnesota, St Paul, Minnesota, USA.
³ Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, USA.
⁴ Department of Clinical Pathology, School of Medicine, Mansoura University, Mansoura, Egypt.
⁵ Center for Mass Spectrometry and Proteomics, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA.
⁶ Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Background: The etiology of dental caries remains poorly understood. With the advent of next-generation sequencing, a number of studies have focused on the microbial ecology of the disease. However, taxonomic associations with caries have not been consistent. Researchers have also pursued function-centric studies of the caries microbial communities aiming to identify consistently conserved functional pathways. A major question is whether changes in microbiome are a cause or a consequence of the disease. Thus, there is a critical need to define conserved functional signatures at the onset of dental caries.

Methods: Since it is unethical to induce carious lesions clinically, we developed an innovative longitudinal ex-vivo model integrated with the advanced non-invasive multiphoton second harmonic generation bioimaging to spot the very early signs of dental caries, combined with 16S rRNA short amplicon sequencing and liquid chromatography-mass spectrometry-based targeted metabolomics.

Findings: For the first time, we induced longitudinally monitored caries lesions validated with the scanning electron microscope. Consequently, we spotted the caries onset and, associated with it, distinguished five differentiating metabolites - Lactate, Pyruvate, Dihydroxyacetone phosphate, Glyceraldehyde 3-phosphate (upregulated) and Fumarate (downregulated). Those metabolites co-occurred with certain bacterial taxa; Streptococcus, Veillonella, Actinomyces, Porphyromonas, Fusobacterium, and Granulicatella, regardless of the abundance of other taxa.

Interpretation: These findings are crucial for understanding the etiology and dynamics of dental caries, and devising targeted interventions to prevent disease progression.

Keywords: Dental caries; Non-invasive bioimaging; genomics; longitudinal model; metabolomics; signatures.

Grants and funding

This work was supported by the the National Institute for Dental and Craniofacial Research of the National Institutes of Health [R90-DE023058]; the National Institute for Dental and Craniofacial Research of the National Institutes of Health [R01-DE026117]; the College of Food Agriculture and Natural resource Science, at the University of Minnesota;.