Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice
Ingestion of Porphyromonas gingivalis exacerbates colitis via intestinal epithelial barrier disruption in mice
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DOI：
10.1111/jre.12816
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发表时间：
2021-01-29
影响因子：
3.5
通讯作者：
Yamazaki, Kazuhisa
中科院分区：
文献类型：
--
作者：
Tsuzuno, Takahiro;Takahashi, Naoki;Yamazaki, Kazuhisa
目的 本研究旨在评估摄入的牙周病原体对小鼠实验性结肠炎的影响，并阐明其潜在机制。 背景 炎症性肠病（IBD）被定义为导致胃肠道损伤的慢性肠道炎症。流行病学研究表明 IBD 与牙周炎之间存在关联。尽管大量摄入的口腔细菌不断到达胃肠道，但摄入的牙周病原菌对肠道炎症的影响仍不清楚。方法通过在小鼠饮用水中加入右旋糖酐硫酸钠溶液诱发实验性结肠炎。实验期间每天口服主要牙周病原体（牙龈卟啉单胞菌、中间普氏菌和具核梭杆菌）。比较各组之间结肠炎的严重程度。对肠上皮细胞系进行体外研究，探讨牙周病原体影响结肠炎发生的分子机制。结果在DSS诱导的结肠炎模型中，与其他病原体相比，口服牙龈卟啉单胞菌显着增加了结肠炎的严重程度。摄入的牙龈卟啉单胞菌通过降低体内紧密连接蛋白的表达来破坏结肠上皮屏障。使用肠上皮细胞系的体外渗透性测定表明牙龈卟啉单胞菌特异性上皮屏障破坏。使用缺乏牙龈蛋白酶的牙龈卟啉单胞菌暗示牙龈蛋白酶可能参与结肠炎的恶化。结论牙龈卟啉单胞菌通过直接与易感宿主的肠上皮屏障相互作用而加剧胃肠道炎症。
Objective This study aimed to evaluate the effects of ingested periodontal pathogens on experimental colitis in mice and to elucidate its underlying mechanisms.Background Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation that results in damage to the gastrointestinal tract. Epidemiological studies have shown an association between IBD and periodontitis. Although a large number of ingested oral bacteria reach gastrointestinal tract constantly, the effect of ingested periodontal pathogens on intestinal inflammation is still unknown.Methods Experimental colitis was induced by inclusion of dextran sodium sulfate solution in drinking water of the mice. Major periodontal pathogens (Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum) were administered orally every day during the experiment. The severity of colitis between the groups was compared. In vitro studies of the intestinal epithelial cell line were conducted to explore the molecular mechanisms by which periodontal pathogens affect the development of colitis.Results The oral administration of P. gingivalis significantly increased the severity of colitis when compared to other pathogens in the DSS-induced colitis model. The ingested P. gingivalis disrupted the colonic epithelial barrier by decreasing the expression of tight junction proteins in vivo. In vitro permeability assays using the intestinal epithelial cell line suggested the P. gingivalis-specific epithelial barrier disruption. The possible involvement of gingipains in the exacerbation of colitis was implied by using P. gingivalis lacking gingipains.Conclusion Porphyromonas gingivalis exacerbates gastrointestinal inflammation by directly interacting with the intestinal epithelial barrier in a susceptible host.