Functional signatures of ex-vivo dental caries onset

Dina G. Moussa, Ashok Kumar Sharma, Tamer A. Mansour, Bruce Witthuhn, Jorge Perdigão, Joel D Rudney, Conrado Aparicio, Andres Gomez

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article number2123624
JournalJournal of Oral Microbiology
Issue number1
StatePublished - 2022

Bibliographical note

Funding Information:
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;. The authors acknowledge Julie Kirihara from the University of Minnesota Spectrometry and Proteomics Center for helping in optimizing the metabolites extraction protocols specifically customized for central carbon metabolism byproducts. The authors thank Kayla Law, Kylene Guse, and Samuel Davison from Gomez lab for helping in processing the 16S rRNA row data, MetaboAnalyst software orientation and technical support for the DNA samples tracking and submission to the genomics center, respectively. MP-SHG imaging was performed at the University of Minnesota Imaging Centers ( with the assistance of Jason Mitchell. The authors thank the labs of Dr. Mansky, Dr. Herzberg, and Dr. Jensen for their lab resources they provide for the DNA and metabolites extraction as well as Dr. Carrera and Mrs. Chen from Dr. Rudney’s lab for helping in collecting the molars and managing the supragingival dental plaque microcosms.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


  • Dental caries
  • Non-invasive bioimaging
  • genomics
  • longitudinal model
  • metabolomics
  • signatures


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