Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of OMS and Periodontology, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, Brazil.
J Clin Periodontol. 2019 Aug;46(8):819-829. doi: 10.1111/jcpe.13151. Epub 2019 Jun 25.
The purpose of this study was to determine inflammatory and epigenetic features following induction of oral and gut dysbiosis in experimental periodontitis in order to examine the interplay between oral and systemic infection.
Periodontitis was induced in 6- to 8-week-old C57BL/6 mice by (a) Ligature placement (Lig group) (oral challenge); (b) P. gingivalis gavage (Pg group) (systemic challenge); and (c) the combination of the two models oral and systemic challenge (Pg + Lig). The duration of the experiment was 60 days, and the animals were then sacrificed for analyses. Alveolar bone loss was assessed, and a multiplex immunoassay was performed. Maxillae and gut tissues were immunostained for DNMT3b (de novo methylation marker), B and T lymphocyte attenuator (BTLA) and IL-18R1 (inflammation markers).
Pg and Pg + Lig groups exhibited higher bone loss when compared to Sham. BAFF, VEGF, RANKL, RANTES and IP-10 were significantly higher with Pg gavage. Likewise, DNMT3b was overexpressed in both gut and maxilla after the Pg administration. The same pattern was observed for BTLA and IL-18R1 in gut tissues.
The systemic microbial challenge either alone or in combination with local challenge leads to distinct patterns of inflammatory and epigenetic features when compared to simply locally induced experimental periodontitis.
本研究旨在确定实验性牙周炎中口腔和肠道菌群失调诱导后炎症和表观遗传特征,以研究口腔和全身感染之间的相互作用。
通过(a)结扎放置(Lig 组)(口腔挑战);(b)牙龈卟啉单胞菌灌胃(Pg 组)(全身挑战);和(c)两种模型口腔和全身挑战的组合(Pg+Lig),在 6 至 8 周龄 C57BL/6 小鼠中诱导牙周炎。实验持续 60 天,然后处死动物进行分析。评估牙槽骨丧失,并进行多重免疫分析。对 DNMT3b(从头甲基化标记物)、B 和 T 淋巴细胞衰减器(BTLA)和 IL-18R1(炎症标志物)进行 maxilla 和肠道组织免疫染色。
与 Sham 相比,Pg 和 Pg+Lig 组的骨损失更高。Pg 灌胃后 BAFF、VEGF、RANKL、RANTES 和 IP-10 显著升高。同样,Pg 给药后肠道和 maxilla 中 DNMT3b 过度表达。肠道组织中也观察到 BTLA 和 IL-18R1 的相同模式。
与单纯局部诱导的实验性牙周炎相比,全身性微生物挑战单独或与局部挑战联合使用会导致明显不同的炎症和表观遗传特征模式。