Periodontitis (PD) potentiates systemic inflammatory diseases and fuels a feed-forward loop of pathogenic inflammation in obesity and type 2 diabetes (T2D). Published work in this area often conflates obesity with obesity-associated T2D; thus, it remains unclear whether PD similarly affects the inflammatory profiles of these 2 distinct systemic diseases. We collected peripheral blood mononuclear cells (PBMCs) from cross-sectionally recruited subjects to estimate the ability of PD to affect cytokine production in human obesity and/or T2D. We analyzed 2 major sources of systemic inflammation: T cells and myeloid cells. Bioplex quantitated cytokines secreted by PBMCs stimulated with T cell– or myeloid-targeting activators, and we combinatorially analyzed outcomes using partial least squares discriminant analysis. Our data show that PD significantly shifts peripheral T cell– and myeloid-generated inflammation in obesity. PD also changed myeloid- but not T cell–generated inflammation in T2D. T2D changed inflammation in samples from subjects with PD, and PD changed inflammation in samples from subjects with T2D, consistent with the bidirectional relationship of inflammation between these 2 conditions. PBMCs from T2D subjects with stage IV PD produced lower amounts of T cell and myeloid cytokines compared with PBMCs from T2D subjects with stage II to III PD. We conclude that PD and T2D affect systemic inflammation through overlapping but nonidentical mechanisms in obesity, indicating that characterizing both oral and metabolic status (beyond obesity) is critical for identifying mechanisms linking PD to systemic diseases such as obesity and T2D. The finding that stage IV PD cells generate fewer cytokines in T2D provides an explanation for the paradoxical findings that the immune system can appear activated or suppressed in PD, given that many studies do not report PD stage. Finally, our data indicate that a focus on multiple cellular sources of cytokines will be imperative to clinically address the systemic effects of PD in people with obesity.

中文翻译：

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牙周炎和糖尿病对肥胖患者的炎症影响不同


牙周炎 （PD） 会加剧全身性炎症性疾病，并助长肥胖和 2 型糖尿病 （T2D） 中致病性炎症的前馈循环。该领域已发表的工作经常将肥胖与肥胖相关的 T2D 混为一谈;因此，目前尚不清楚 PD 是否同样影响这 2 种不同的全身性疾病的炎症特征。我们从横断面招募的受试者中收集了外周血单核细胞 （PBMC），以估计 PD 影响人类肥胖和/或 T2D 中细胞因子产生的能力。我们分析了全身炎症的 2 个主要来源：T 细胞和骨髓细胞。Bioplex 定量了 T 细胞或骨髓靶向激活剂刺激的 PBMC 分泌的细胞因子，我们使用偏最小二乘判别分析组合分析了结果。我们的数据显示，PD 显着改变了肥胖症中外周 T 细胞和骨髓产生的炎症。PD 还改变了 T2D 中髓细胞产生的炎症，但没有改变 T 细胞产生的炎症。T2D 改变了 PD 受试者样本中的炎症，而 PD 改变了 T2D 受试者样本中的炎症，这与这两种情况之间炎症的双向关系一致。与患有 II 期至 III 期 PD 的 T2D 受试者的 PBMC 相比，患有 IV 期 PD 的 T2D 受试者产生的 T 细胞和髓系细胞因子的量较低。我们得出结论，PD 和 T2D 通过肥胖中重叠但不相同的机制影响全身炎症，表明表征口腔和代谢状态（超越肥胖）对于确定将 PD 与肥胖和 T2D 等全身性疾病联系起来的机制至关重要。 鉴于许多研究没有报告 PD 分期，IV 期 PD 细胞在 T2D 中产生较少细胞因子的发现为免疫系统在 PD 中可能出现激活或抑制的矛盾发现提供了解释。最后，我们的数据表明，关注细胞因子的多种细胞来源对于临床解决 PD 对肥胖患者的全身影响至关重要。