FIG. 1. Oral mucosal breaks trigger systemic inflammatory responses.

(A) Experimental workflow. (B) Inferred relative bacterial abundances from eight HMP body sites (n=336). (C) Body site inferred relative abundances for timepoints from RA patients with and without periodontal disease, median. (D) Inferred relative oral abundances in blood for one RA donor with and one without periodontal disease. (E) Relative abundances of bacteria genera from oral brushings (left) and blood (right). (F) Log₁₀ adjusted p-values versus log-fold changes of human gene expression relative to bacterial abundances of the three oral body-sites. (G) Enriched GO pathways in differentially expressed human genes from (F) (adjusted p-values). (H) Percent monocytes in blood cell counts compared to inferred relative abundances of oral bacteria, Pearson’s correlation. (I-J) RT-qPCRs of mRNA of inflammatory genes in (I) whole blood, (J) granulocytes, monocytes, lymphocytes (n=4–6) stimulated with oral bacteria vs. unstimulated control. (K) Flow cytometry data showing proportion of ISG15⁺ monocytes in CD14⁺ monocytes incubated with PBS, oral bacteria, and anti-FcγR2a or isotype (n=8). (B), (H), (I), two-tailed Kruskal-Wallis test, Dunnett’s-corrected for multiple comparisons. (C), Mann-Whitney U test. (K), within-subjects ANOVA, Tukey-corrected for multiple comparisons. Mean ± SD *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001 or exact value shown.