Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring.

Pune N Paqué,Wendy E Kaman,Florian J Wegehaupt,Christopher Herz,Michal Karpíšek,Joël S Jenzer,Konstantinos Mitsakakis,Daniel B Wiedemeier,Patrick R Schmidlin,Nagihan Bostanci,Thomas Thurnheer,Georgios N Belibasakis,Philipp Körner,Thomas Attin,Johannes R Peham,Kai Bao,John P Hays

doi:10.3390/jpm11030235

Abstract

This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.

Highlights

The primary goal in dental medicine is the maintenance of oral health and the prevention of oral diseases, such as caries or periodontitis [1]
It can be seen that data for A. actinomycetemcomitans, S. sobrinus, and oral Lactobacilli were below the detection limit in the majority of the subjects
The current research identified four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) that enabled the correct diagnosis of dental caries in 37 out of 38 patients using random forest (RF) analysis

Summary

Introduction

The primary goal in dental medicine is the maintenance of oral health and the prevention of oral diseases, such as caries or periodontitis [1]. The close proximity of odontoblasts and the dental pulp to the lesions causes host immune responses that lead to the production and release of several cytokines, chemokines, and growth factors [22]. Both the gingivitis and the caries inflammatory responses take place in the presence of saliva throughout the oral cavity. Thereby, this oral fluid acts as a collection matrix for released immune defense molecules and microorganisms in both diseases

Methods

Results

Discussion

Conclusion