The Impact of Race/Ethnicity on Inflammation Regulation and Microbiome Interactions in Periodontitis

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Project Summary/ Abstract In the United States, the prevalence of periodontitis is greatest in Mexican Americans (59.7%) and non-Hispanic Blacks (56.6%). Severe periodontitis is also more prevalent in these populations; non-Hispanic Blacks (14.7%) and Mexican Americans (13.4%). Although race and ethnicity are associated with periodontal disease prevalence and severity, there is lack of convincing evidence of biological factors explaining the differences. Specialized pro-resolving mediators (SPMs) induce resolution of inflammation by actively regulating cellular activity of immune cells and stromal cells signaling through specific G protein–coupled receptors. Resolution of inflammation induced by SPMs reverses dysbiotic shifts of the oral microbiota in experimental periodontitis models. SPMs and SPM pathway markers are associated with clinical periodontitis and abnormalities in SPM production and function in forms of periodontitis disproportionately affecting certain racial/ethnic groups. The impact of race/ethnicity in resolution of inflammation in severe periodontitis has not been investigated. This study aims to investigate molecular profiles of resolution of inflammation in Mexican Americans with severe periodontitis. Four subject groups will be recruited; Mexican Americans and White Americans with severe periodontitis (generalized, stage III/ IV, grade B/C), Mexican American and White American healthy controls. The hypothesis, supported by our preliminary data, is that Mexican Americans with severe periodontitis will exhibit distinct profiles of lipid mediators that promote inflammation, including SPMs, SPM pathway markers as well as pro-inflammatory lipid mediators, SPM receptors, and an associated subgingival microbiome dysbiosis, compared to White Americans. The following specific aim is proposed: Characterize the local and systemic profiles of SPMs, SPM pathway markers, SPM receptors and the subgingival microbiome in Mexican Americans and White Americans with severe periodontitis. We plan to analyze lipid mediator levels, SPM receptor expression and the subgingival microbiome in multiple biological specimens including gingiva, plasma, serum, neutrophils, monocytes and subgingival plaque. Correlations between lipid mediator levels, receptor expression and relative bacterial abundance will be analyzed with the Data Integration Analysis for Biomarker discovery using a Latent compOnents (DIABLO) method, which can identify key molecules or microorganisms associated with resolution of periodontal inflammation which cannot be identified by traditional statistical methods. We expect that local and systemic resolution of inflammation profiles and composition of the subgingival microbiome in Mexican Americans will be different from those in White Americans. The correlation signatures between lipid mediator, SPM receptor and subgingival microbiome in these subjects will also be distinct. These results will advance the understanding of the role of resolution of inflammation in disease disparities. The identified molecules or microorganisms in the correlation analysis can be targeted for novel therapy development.