TABLE 1.

Caries-causing factors.

Perspective			Representatives	Molecular mechanism	Specific regulatory factors	References
Ecological perspectives	The caries ecological hypothesis		Glucan production	Gtf-derived dextran helps to accumulate bacterial cells	Gtf	Falsetta et al., 2014
			Bacterial-fungal sugar metabolism	Candida albicans induces the expression of S. mutans virulence genes and enhances plaque Gtf activity	Candida albicans, S. mutans
			Colonization of acidic dominant flora	The microenvironment in the mouth is changed, acidity is increased, acid-resistant bacteria are colonized, and the environment is driven to an acidic state	Acidic bacteria
	Genetic factors		Low caries gene loci	Mutations in the genes of organic matrix molecules can lead to the production or absence of abnormal proteins, resulting in mineralization defects, affecting bacterial adhesion or resistance to acidic environments, increasing tooth sensitivity and thus leading to dental caries	5q13.3, 14q11.2, Xq27.1	Opal et al., 2015
			High caries gene loci		13q31.1, 14q24.3
			Immune response	Modification of caries susceptibility through immune response	Gene Fragments HLA-DR4, DR3, TNFα117	Vieira, 2012
					Major histocompatibility complexes
			SCPP gene	SPP1 encodes a protein that is expressed in tissues and is involved in mineralized tissue remodeling (Hasan et al., 2022)	SPP1, MEPE, IBSP, DMP1, DSPP	Eckert et al., 2017
Microbiological perspective	Bacterium	Traditional cariogenic bacteria	Streptococcus mutans	Colonizes the tooth surface and participates in interspecies competition within the plaque biofilm, which in turn leads to biofilm alteration	Gbp, EPS
		Symbiotic cariogenic bacteria	Streptococcus sobrinus	Forming a cariogenic microenvironment with other streptococci	ComRS systems	Underhill et al., 2018
			Streptococcus sanguinis	Hydrogen peroxide produced by blood streptococci provides an acidic environment for cariogenesis	Hydrogen peroxide
		Other bacteria	Lactobacillus	Promotes bacterial attachment to tooth surfaces, promotes plaque build-up and limits organic acids	water-insoluble polysaccharide
			Streptococcus pyogenes	Formation of microenvironment-dependent host-pathogen protein complexes	GlycerAldehyde 3-Phosphate DeHydrogenase (GADPH)	Chaudhary et al., 2021
			Streptococcus Gordonii	Produces alkali, regulates pH fluctuations in the mouth, adheres to dental plaque, and works in conjunction with other cariogenic bacteria	ATP-binding cassette (ABC)-type transporters
			Streptococcus constellatus	In case of septic infection of the tooth
			Streptococcus pharyngitis	Acidic bacteria colonize in an acidic environment
	Cariogenic fungi		Candida albicans	Bacterial-fungal co-interaction