牙周炎与炎症性肠病相关研究进展

Research progress on association between periodontitis and inflammatory bowel disease

炎症性肠病(inflammatory bowel disease,IBD)是一组受多种因素影响的慢性非特异性胃肠道炎症性疾病,主要包括克罗恩病和溃疡性结肠炎。牙周炎是一类以牙菌斑生物膜为始动因子,牙槽骨慢性吸收破坏为表现的疾病。近年来越来越多的研究表明牙周炎与炎症性肠病二者之间存在相关性,但两者间的关系仍不明确。本综述从流行病学证据、生物学证据、关联治疗证据三个维度探究了两种疾病的内在关系:从流行病学证据来看,牙周炎与IBD患病风险增加相关,反过来IBD也影响牙周健康,其双向关联还需要进一步扩大数据源研究;从生物学证据来看,无论临床研究还是动物实验均说明IBD和牙周炎相互影响;从关联治疗证据来看,对IBD治疗有益的药物用于牙周炎的防治同样有效,对牙周炎改善有利的药物也可明显缓解IBD。IBD与牙周炎的相互作用机制包括微生物途径和免疫途径。微生物途径是指由于牙周炎患者口腔内机会致病菌的比例增加以及IBD影响了胃液分泌以及肠道菌群平衡,口腔细菌通过口腔肠道轴或血行传播异位定植于肠道的几率增大,这些微生物会通过释放毒力因子,破坏肠道黏膜屏障,引发炎症反应等方式进一步加重IBD炎症。免疫途径是指牙周炎激活口腔内适应性免疫,产生大量免疫细胞,特别是Th17细胞,其表面存在肠道归巢标记物α4β7整合素,IBD患者肠道黏膜上的α4β7整合素的配体表达增加,使得口腔Th17细胞加速转移至肠道从而加剧肠道炎症。研究表明,IBD患者口腔内细胞因子的表达量异常,如肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-10、白细胞介素-6、白细胞介素-21、可溶性CD40配体(soluble CD40 ligand,sCD40L)、白细胞介素-23和干扰素-γ,提示IBD通过免疫途径影响牙周炎,以上细胞因子是治疗两种疾病的靶点所在,可为未来两种疾病的防治提供研究方向。

Inflammatory bowel disease(IBD)is a group of chronic,non-specific inflammatory diseases of the gastrointestinal tract including primarily Crohn's disease and ulcerative colitis,which are affected by multiple factors.Periodontitis is a type of disease characterized by plaque biofilm as the initiating factor and chronic destruction of alveolar bone via resorption.An increasing number of studies have reported a correlation between periodontitis and IBD,but the relationship between the two remains unclear.In this study,we explore the internal relationships between the two diseases from three dimensions,including epidemiological,biological,and associated treatment evidence.Based on epidemiological evidence,periodontitis was found to be associated with an increased risk of IBD,which also affects periodontal health,although the bidirectional correlation needs to be further studied by expanding the number of data sources.From the biological evidence,both clinical studies and animal experiments show that IBD and periodontitis are interconnected.Based on evidence from association therapy,drugs that are beneficial for the treatment of IBD are also effective in the prevention and treatment of periodontitis.In addition,drugs that are good for improving periodontitis can also significantly alleviate IBD.The interaction mechanism between IBD and periodontitis includes the microbial pathway and the immunization route.The microbial pathway refers to the increase in the probability of intestinal tract ectopic colonization by oral bacteria transmitted through the mouth-gut axis or blood,resulting from the increase in the proportion of opportunistic pathogens in the oral cavity of patients with periodontitis and the influence of IBD on the secretion of gastric juice and the balance of intestinal flora.These microorganisms further aggravate IBD inflammation by releasing virulence factors,destroying the intestinal mucosal barrier,and triggering inflammatory responses.In periodontitis,adaptive immunity is activated in the mouth,leading to the production of a large number of immune cells,including Th17 containing the intestinal homing markerα4β7 integrin on their surface.Increased ligand expression ofα4β7 integrin in the intestinal mucosa of patients with IBD accelerates oral Th17 cell transfer to the intestine,thereby worsening intestinal inflammation.In parallel,the abnormal expression of cytokines,such as TNF-α,IL-1β,IL-10,IL-6,IL-21,soluble CD40 ligand(sCD40L),IL-23,and INF-γ,in the oral cavity of patients with IBD was observed,suggesting that IBD may affect periodontitis through immunity.These cytokines represent targets for the treatment of both diseases and provide a research direction for their prevention and treatment in the future.