Work

Cariogenic microorganisms induce oral epithelial atypia through host-microbiome-high sugar diet interactions

Year: 2026

Type: article

Abstract: Oral mucosal development during infancy is crucial because disruptions at this stage can compromise barrier function and increase susceptibility to oral diseases throughout life. The contribution of oral pathogens to oral mucosal development in infancy remains poorly understood. Here, we show that early-life co-infection with Streptococcus mutans and Candida albicans under a sucrose-enriched diet perturbs oral epithelial homeostasis and is associated with atypical hyperplasia and parakeratosis of the tongue. Using an infant rat model, we utilized OMICS data (microbiome, untargeted metabolomics, and multiplex immune profiling) together with high-dimensional mediation statistic modeling to reveal that microbial co-infection synergizes with dietary sugar to shape oral and gut microbial communities. The microbial alterations were accompanied by systemic metabolic alterations, marked by enhanced amino acid and carbohydrate metabolism, and depletion of vitamin B6 and taurine pathways. Oral microbial and metabolic changes were associated with atypical hyperplasia and parakeratosis on both dorsal and ventral surfaces of tongue mucosa. Complementary in vitro modeling revealed that sucrose-conditioned co-infection disrupted epithelial barrier integrity and orchestrated metabolic remodeling in oral epithelial cells. These findings reveal a host-microbe-diet interaction axis underlying early mucosal remodeling and provide mechanistic insight into how cariogenic microbes may influence oral mucosal disease beyond caries.

Source: npj Biofilms and Microbiomes

DOI: 10.1038/s41522-026-00987-9