Biosynthetic Gene Cluster Muf in Streptococcus mutans Predicts Longitudinal Caries Progression in Young Children

ABSTRACT Background Streptococcus mutans ( S. mutans ) is a primary etiological agent in dental caries. However, longitudinal evidence regarding its role in caries initiation and progression remains limited. This study aimed to evaluate the utility of the muf biosynthetic gene cluster (BGC) in S. mutans as a predictor of caries occurrence and progression. Methods We first conducted a case–control study to assess the prevalence of the muf BGC using quantitative polymerase chain reaction (qPCR). Subsequently, a prospective cohort study was performed to evaluate the cariogenic potential of muf . Caries increment over the follow‐up period was compared between children harboring muf ‐positive and muf ‐negative S. mutans . Results Initial screening targeting the glucosyltransferase B (gtfB) gene confirmed the presence of S. mutans . Among the 46 S. mutans ‐positive specimens, the prevalence of the muf locus was higher in children with caries (44.12%, 15/34) than in caries‐free controls (16.67%, 2/12), corresponding to an odds ratio (OR) of 3.95. In the prospective cohort of 119 children, univariate analysis revealed that muf ‐positivity was associated with a 2.13‐fold increased risk of caries increment over the 6‐month follow‐up (60.7% vs. 28.6%, p < 0.01). Importantly, this association remained robust after multivariable adjustment for potential confounders, with muf ‐positivity continuing to confer nearly twice the risk of developing new carious lesions ( p < 0.01). Furthermore, an integrated risk stratification framework identified the double‐positive ( muf + /gtfB + ) genotype as a high‐risk factor for caries progression, yielding an RR of 6.21 compared to the muf − /gtfB − baseline. Conclusions BGC m uf ‐positive S. mutans is associated with increased caries progression in early childhood, highlighting its potential as a biomarker for identifying high‐risk individuals.