The Discovery, Biological Evaluations, and Modified Applications of Metabolite Avhs Derived from Dental Plaque Biofilms

Abstract

The present study aimed to identify the “dominant metabolite” from plaque biofilm of children with different levels of dental caries, to assess the biological properties of “dominant metabolite” and modify it for anticariogenic applications. The preschool children were divided into caries free (CF) group, early childhood caries (ECC) group and severe early childhood caries (SECC) group using a case-control study. Untargeted metabolomics was used to detect “dominant metabolite” among three groups. The biological properties of “the dominant metabolite” was evaluated by biocompatibility analysis, recording the growth and acid production curves of Streptococcus mutans (S. mutans), remineralization effect and biofilm targeting tests. For endowing “the dominant metabolite” with anti-biofilm and anticariogenic effect, antibacterial peptide was modified with it and anticariogenic effect was assessed in vivo. The results showed that a total of 102 children aged 36 months were included with 34 children each group. Metabolomics results showed that Ala-Val-His-Ser (AVHS) was the most abundant metabolites in CF group (P<0.05) and had the best predictive performance for healthy children (AUC=0.675). AVHS was found to have good biocompatibility, slow down the growth and acid production rate of S. mutans, target plaque biofilm in vitro. AVHS modified with RWWRWW (AVHS@RWWRWW) presented antibiofilm effects and preventive effect on dental caries of rats in vivo (P<0.05). In conclusion, AVHS not only has the best predictive performance for healthy children in clinical research but owed multiple biological performances, modified with RWWRWW enhancing its antibiofilm and anticariogenic effects, which can be further developed as a promising antimicrobial agent.

Note:
Funding Information: This study was supported by grants from the Hong Kong Macao Taiwan Science and Technology Cooperation Project of Shanghai Municipal Science and Technology Commission (Project No. 22410760200), Opening Research Fund from Shanghai Key Laboratory of Stomatology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine (Project No. 2022SKLS-KFKT010).

Conflict of Interests: The authors declare no competing interests.

Ethical Approval: All guardians of the children provided their written informed consent, and the study protocol was approved by the Institutional Review Board of the Ninth People’s Hospital School of Medicine (SH9H-2019-A340-1).

Keywords: early childhood caries, plaque biofilms, metabolomics, antimicrobial peptide