Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Periodontal Res. 2021 Apr;56(2):275-288. doi: 10.1111/jre.12816. Epub 2021 Jan 29.
This study aimed to evaluate the effects of ingested periodontal pathogens on experimental colitis in mice and to elucidate its underlying mechanisms.
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.
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.
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.
Porphyromonas gingivalis exacerbates gastrointestinal inflammation by directly interacting with the intestinal epithelial barrier in a susceptible host.
本研究旨在评估摄取的牙周病原体对实验性结肠炎小鼠的影响，并阐明其潜在机制。
炎症性肠病（IBD）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进入胃肠道，但摄取的牙周病原体对肠道炎症的影响尚不清楚。
通过在小鼠饮用水中加入葡聚糖硫酸钠溶液来诱导实验性结肠炎。在实验过程中，每天口服给予主要牙周病原体（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。通过体外肠上皮细胞系研究探索牙周病原体影响结肠炎发展的分子机制。
与 DSS 诱导的结肠炎模型中的其他病原体相比，牙龈卟啉单胞菌的口服给药显著增加了结肠炎的严重程度。摄取的牙龈卟啉单胞菌通过体内降低紧密连接蛋白的表达破坏了结肠上皮屏障。使用肠上皮细胞系进行的体外通透性测定表明，牙龈卟啉单胞菌具有特异性的上皮屏障破坏作用。通过使用缺乏牙龈蛋白酶的牙龈卟啉单胞菌，暗示了牙龈蛋白酶可能参与了结肠炎的加重。
在易感宿主中，牙龈卟啉单胞菌通过与肠道上皮屏障直接相互作用，加剧胃肠道炎症。
