Investigating Metabolic Trends in the Oral Cavity to Identify Novel Metabolites

Abstract The human oral microbiome typically contains over 700 different microbial species. These interactions between the microorganisms within this community can shape the microenvironment throughout the human body, as these interactions are paramount to maintaining oral and overall systemic health. Recent advances in technology, such as next-generation sequencing (NGS), have revealed the complexities of the oral microbiome, linking dysbiosis of the oral microbiome with several chronic ailments such as cardiovascular disease, diabetes, and inflammatory bowel disease. However, the role of microbial secondary metabolites in oral and systemic disease progression remains poorly understood. Here, we conducted a metabolomics study on the human salivary secondary metabolome during the induction of gingival inflammation (gingivitis), the precursor to periodontal disease. In this study, we sought to assess the changes in the oral secondary metabolome during disease progression by emulating dysbiosis of the oral microbiome through a twenty-one-day induction of gingivitis in twenty human participants. We identified secondary metabolites, cyclo(L-Tyr-L-Pro) with regulatory properties for quorum sensing and inflammatory marker secretion, indicating a specialized role for secondary metabolites in oral health maintenance. Surprisingly, we also uncovered a previously unknown metabolic lag that occurs during dysbiosis recovery of the oral cavity, which indicates a lingering presence of signaling molecules for pathogenic microbe proliferation or a total oral metabolome modification following microenvironmental stress in the oral cavity. This work represents a high-resolution metabolomic landscape for understanding oral health during gingivitis that opens new opportunities for combating progressive periodontal diseases and sepsis due to the translocation of oral microbes in the human body.