Randall David, Alsam Asil, Kieswich Julius, Joseph Susan, Aduse-Opoku Joseph, Swann Jonathan, Boyde Alan, Davis Graham, Mills David, McCafferty Kieran, Curtis Michael, Yaqoob Muhammed M
William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK.
Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK.
Nephrol Dial Transplant. 2025 May 30;40(6):1187-1202. doi: 10.1093/ndt/gfae266.
It is presently unclear why there is a high prevalence of periodontal disease in individuals living with chronic kidney disease. Whilst some have argued that periodontal disease causes chronic kidney disease, we hypothesized that alterations in saliva and the oral microenvironment in organisms with kidney disease may initiate periodontal disease by causing dysbiosis of the oral microbiota.
Experimental kidney disease was created using adenine feeding and subtotal nephrectomy in rats, and by adenine feeding in mice. Loss of periodontal bone height was assessed using a dissecting microscope supported by micro-CT, light, confocal and electron microscopy, and immunohistochemistry. Salivary biochemistry was assessed using NMR spectroscopy. The oral microbiome was evaluated using culture-based and molecular methods, and the transmissibility of dysbiosis was assessed using co-caging and microbial transfer experiments into previously germ-free recipient mice.
We demonstrate that experimental kidney disease causes a reproducible reduction of alveolar bone height, without gingival inflammation or overt hyperparathyroidism but with evidence of failure of bone formation at the periodontal crest. We show that kidney disease alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from animals with kidney disease displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. Co-housing diseased rats with healthy ones ameliorates the periodontal disease phenotype, whilst transfer of oral microbiota from mice with kidney disease causes periodontal disease in germ-free animals with normal kidney function.
We advocate that periodontal disease should be regarded as a complication of kidney disease, initiated by oral dysbiosis through mechanisms independent of overt inflammation or hyperparathyroidism.
目前尚不清楚为何慢性肾脏病患者中牙周疾病的患病率较高。虽然有人认为牙周疾病会导致慢性肾脏病，但我们推测，肾脏病患者唾液和口腔微环境的改变可能通过引起口腔微生物群失调而引发牙周疾病。
通过给大鼠喂食腺嘌呤并进行次全肾切除术，以及给小鼠喂食腺嘌呤来制造实验性肾脏病。使用解剖显微镜，并辅以显微CT、光学显微镜、共聚焦显微镜和电子显微镜以及免疫组织化学，评估牙周骨高度的丧失情况。使用核磁共振波谱法评估唾液生物化学。使用基于培养的方法和分子方法评估口腔微生物群，并通过同笼饲养和将微生物转移到先前无菌的受体小鼠体内的实验，评估失调的可传播性。
我们证明，实验性肾脏病会导致牙槽骨高度可重复降低，无牙龈炎症或明显的甲状旁腺功能亢进，但有牙周嵴处骨形成失败的证据。我们表明，肾脏病会改变唾液的生化成分，并诱导口腔微生物群逐渐失调，患有肾脏病的动物的微生物样本显示总体细菌生长减少、α多样性增加、健康口腔微生物群的关键成分（如链球菌和罗氏菌）丰度降低，以及包括革兰氏阴性菌门变形菌和拟杆菌的次要分类群增加。将患病大鼠与健康大鼠同笼饲养可改善牙周疾病表型，而将患有肾脏病的小鼠的口腔微生物群转移到肾功能正常的无菌动物体内会导致牙周疾病。
我们主张应将牙周疾病视为肾脏病的一种并发症，它是由口腔失调通过独立于明显炎症或甲状旁腺功能亢进的机制引发的。
