한빛사논문
Yuan Liu 1†, Scott G. Daniel 2†, Hye‑Eun Kim 1, Hyun Koo 3,4, Jonathan Korostof 5, Flavia Teles 4,6, Kyle Bittinger 2* and Geelsu Hwang 1,4,7*
1Department of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2Department of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
3Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4Center for Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
5Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
6Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
7Department of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, Seoul 03722, Republic of Korea.
†Yuan Liu and Scott G. Daniel contributed equally to this work.
*Corresponding author: correspondence to Kyle Bittinger or Geelsu Hwang
Abstract
Background
Dental caries is a microbe and sugar-mediated biofilm-dependent oral disease. Of particular significance, a virulent type of dental caries, known as severe early childhood caries (S-ECC), is characterized by the synergistic polymicrobial interaction between the cariogenic bacterium, Streptococcus mutans, and an opportunistic fungal pathogen, Candida albicans. Although cross-sectional studies reveal their important roles in caries development, these exhibit limitations in determining the significance of these microbial interactions in the pathogenesis of the disease. Thus, it remains unclear the mechanism(s) through which the cross-kingdom interaction modulates the composition of the plaque microbiome. Here, we employed a novel ex vivo saliva-derived microcosm biofilm model to assess how exogenous pathogens could impact the structural and functional characteristics of the indigenous native oral microbiota.
Results
Through shotgun whole metagenome sequencing, we observed that saliva-derived biofilm has decreased richness and diversity but increased sugar-related metabolism relative to the planktonic phase. Addition of S. mutans and/or C. albicans to the native microbiome drove significant changes in its bacterial composition. In addition, the effect of the exogenous pathogens on microbiome diversity and taxonomic abundances varied depending on the sugar type. While the addition of S. mutans induced a broader effect on Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog abundances with glucose/fructose, S. mutans-C. albicans combination under sucrose conditions triggered unique and specific changes in microbiota composition/diversity as well as specific effects on KEGG pathways. Finally, we observed the presence of human epithelial cells within the biofilms via confocal microscopy imaging.
Conclusions
Our data revealed that the presence of S. mutans and C. albicans, alone or in combination, as well as the addition of different sugars, induced unique alterations in both the composition and functional attributes of the biofilms. In particular, the combination of S. mutans and C. albicans seemed to drive the development (and perhaps the severity) of a dysbiotic/cariogenic oral microbiome. Our work provides a unique and pragmatic biofilm model for investigating the functional microbiome in health and disease as well as developing strategies to modulate the microbiome.
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