**1. Introduction**

Early childhood caries (ECC) is one of the most prevalent infectious diseases affecting around half of children worldwide [1,2]. ECC has been poorly controlled in many countries and has become a serious public-health problem, especially among socially vulnerable groups [3]. A better understanding of the etiology and mechanism can help with the prevention, diagnosis, treatment, and public intervention of this disease and further reduce the socioeconomic burden.

Dental caries including ECC has been considered as a multifactorial disease that is affected by the host genetic status, microorganisms, diet, and time. The etiology of dental caries is chemical-driven to microorganism-driven due to the rapid development of oral microbiology related studies. The dysbiosis of the dental plaque microbiota community could initiate this disease with the presence of fermentable carbohydrates mainly from diet. The affected plaque becomes more acidogenic and acid tolerant, which causes the decrease of local pH. Once the pH is lower than 5.5, the balance between demineralization and remineralization of dental hard tissue breaks down [4]. The continuous demineralization of dental hard tissue could eventually cause the irreversible dental carious lesions.

Preventive methods and treatments focused on traditional cariogenic bacteria like *S. mutans* and *lactobacillus* have shown some effects in clinical studies [5]. However, dental plaque, in which more than 700 different bacterial species have been identified, is one

**Citation:** Chen, J.; Kong, L.; Peng, X.; Chen, Y.; Ren, B.; Li, M.; Li, J.; Zhou, X.; Cheng, L. Core Microbiota Promotes the Development of Dental Caries. *Appl. Sci.* **2021**, *11*, 3638. https://doi.org/10.3390/app11083638

Academic Editor: Yoshiaki Nomura

Received: 21 March 2021 Accepted: 14 April 2021 Published: 18 April 2021

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of the most complex microbiota communities co-existing with the human body, and the dysbiosis of dental plaque can cause diseases just like the gut microbiota [6]. It is increasingly recognized that it is not a specific pathogen, but the interactions among different bacterial species that leads to the physiological functions and pathogenic characteristics of dental plaque [7–9]. In recent years, several studies have demonstrated the existence of core microbiome in dental caries [10,11]. The existence of a "core microbiome" was first proposed by Turnbaugh et al. [12] and referred to the organisms, genes, or functions shared by all or most individuals such as the oral cavity, nasal cavity, skin, and intestinal tract.

A previous longitudinal study about using microbiome as a dental caries indicator has successfully predicted ECC in healthy individuals, and provided evidence that some microbial populations in plaque and saliva changed acutely along with ECC onset, which may be the core microbiota of ECC [13]. This microbiota prediction model can diagnose ECC from a healthy population with 70% accuracy and predict future ECC onset with 81% accuracy. However, the researchers did not conduct studies to verify the composition of core microbiota and its pathogenicity in vivo and in vitro. Therefore, to further explore the cariogenic ability of core microbiota and its impact on previously known cariogenic *S. mutans*, our study established the multiple-species biofilm model with four represented bacteria from the highest predictors of ECC [13] including *Prevotella*, *Leptotrichia*, *Veillonella,* and *Fusobacterium*, cultured with or without *S. mutans* and compared the acid production ability, biofilm structure, EPS synthesis, demineralization ability, and in vivo cariogenic potential on animal model.
