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Meta-analysis of oral microbiome reveals sex-based diversity in biofilms during periodontitis
Rita Del Pinto, Claudio Ferri, Mario Giannoni, Fabio Cominelli, Theresa T. Pizarro, Davide Pietropaoli
Rita Del Pinto, Claudio Ferri, Mario Giannoni, Fabio Cominelli, Theresa T. Pizarro, Davide Pietropaoli
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Research Article Inflammation Microbiology

Meta-analysis of oral microbiome reveals sex-based diversity in biofilms during periodontitis

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Abstract

Sex is an often overlooked, yet compulsory, biological variable when performing biomedical research. Periodontitis is a common yet progressively debilitating chronic inflammatory disorder affecting the tissues supporting teeth that ultimately leads to tooth loss if left untreated. The incidence of periodontitis is sex biased, with increased prevalence in males compared with females but with unknown etiology. We performed a sex-specific meta-analysis using publicly available oral microbiome data from different sampling sites of patients with periodontitis and periodontally healthy controls; sex balance was established for each periodontal health condition. Our results show sex-based diversity in oral biofilms of individuals with periodontitis but not in their saliva, with increased abundance of several periodontal pathogens in subgingival plaques from females compared with males. We devised a quantitative measure, uniquely defined as the Microsexome Index (MSI), which indicates that sexual dimorphism in subgingival bacterial composition is a distinct feature of reduced microbial diversity during periodontitis but not under healthy conditions. In addition, we found that smoking exacerbates microsexome diversity in supragingival biofilms, particularly during periodontitis. Taken together, we provide insights regarding sex-based diversity in periodontitis, a disease with multiorgan associations, and provide the rationale for further mechanistic, diagnostic, and therapeutic studies.

Authors

Rita Del Pinto, Claudio Ferri, Mario Giannoni, Fabio Cominelli, Theresa T. Pizarro, Davide Pietropaoli

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Figure 4

The Microsexome Index (MSI) represents a quantitative measure of sex-specific diversity.

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The Microsexome Index (MSI) represents a quantitative measure of sex-spe...
In order to reduce bias from smoking, MSI was calculated based on subgingival microbiome composition of nonsmokers, excluding individuals with either unknown smoking history or who reported being smokers. (A) Genera differentially abundant between sexes in periodontally healthy individuals and during periodontitis, after applying FDR to 2-tailed t test (31), were used to compute MSI, a summary statistic of observed sex-specific microbial diversity wherein values different from zero indicate increased sex-specific enrichment (left). Violin plots show statistical difference in MSI between sexes by periodontal condition, indicating MSI as a summary measure of sex-predictive power of subgingival microbiome (right). ***P < 0.001; ****P < 0.0001 by Wilcoxon rank-sum test. TM7x, Saccharibacteria. (B) Relationship of MSI with subgingival microbial richness overall (left) and by sex (right), calculated by applying Pearson’s correlation coefficient. Different from periodontally healthy controls (top left), MSI shows significant, inverse relationship with subgingival microbial richness during periodontitis (bottom left). When dissecting information by sex (right), periodontally healthy males uniquely show a significant, direct correlation of MSI with richness. (C) Relationship of MSI and subgingival microbial richness with age by periodontal condition using Pearson’s correlation coefficient, with evidence of a trend toward increased MSI and parallel decrease in richness with age, not observed in healthy controls. (D) Consistent with this, MSI reliably predicts sex in both periodontal conditions, but addition of age increases predictive accuracy only during periodontitis. Data visualization refers to healthy Fs (N = 21), healthy Ms (N = 18), periodontitis Fs (N = 15), and periodontitis Ms (N = 11). AUC-ROC with RF is applied.

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