Liu Sixin, Dashper Stuart G, Zhao Rui
School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Centre for Oral Health Research, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Parkville, Australia.
J Alzheimers Dis. 2023;91(1):129-150. doi: 10.3233/JAD-220627.
Pre-clinical evidence implicates oral bacteria in the pathogenesis of Alzheimer's disease (AD), while clinical studies show diverse results.
To comprehensively assess the association between oral bacteria and AD with clinical evidence.
Studies investigating the association between oral bacteria and AD were identified through a systematic search of six databases PubMed, Embase, Cochrane Central Library, Scopus, ScienceDirect, and Web of Science. Methodological quality ratings of the included studies were performed. A best evidence synthesis was employed to integrate the results. When applicable, a meta-analysis was conducted using a random-effect model.
Of the 16 studies included, ten investigated periodontal pathobionts and six were microbiome-wide association studies. Samples from the brain, serum, and oral cavity were tested. We found over a ten-fold and six-fold increased risk of AD when there were oral bacteria (OR = 10.68 95% CI: 4.48-25.43; p < 0.00001, I2 = 0%) and Porphyromonas gingivalis (OR = 6.84 95% CI: 2.70-17.31; p < 0.0001, I2 = 0%) respectively in the brain. While AD patients exhibited lower alpha diversity of oral microbiota than healthy controls, the findings of bacterial communities were inconsistent among studies. The best evidence synthesis suggested a moderate level of evidence for an overall association between oral bacteria and AD and for oral bacteria being a risk factor for AD.
Current evidence moderately supports the association between oral bacteria and AD, while the association was strong when oral bacteria were detectable in the brain. Further evidence is needed to clarify the interrelationship between both individual species and bacterial communities and the development of AD.
临床前证据表明口腔细菌与阿尔茨海默病(AD)的发病机制有关,而临床研究结果则各不相同。
综合评估口腔细菌与AD之间的关联,并提供临床证据。
通过系统检索六个数据库(PubMed、Embase、Cochrane Central Library、Scopus、ScienceDirect和Web of Science)来识别研究口腔细菌与AD之间关联的研究。对纳入研究进行方法学质量评分。采用最佳证据综合法整合结果。在适用时,使用随机效应模型进行荟萃分析。
纳入的16项研究中,10项研究了牙周致病共生菌,6项是全微生物组关联研究。对来自大脑、血清和口腔的样本进行了检测。我们发现,当大脑中存在口腔细菌(OR = 10.68,95% CI:4.48 - 25.43;p < 0.00001,I² = 0%)和牙龈卟啉单胞菌(OR = 6.84,95% CI:2.70 - 17.31;p < 0.0001,I² = 0%)时,AD风险分别增加了10倍以上和6倍。虽然AD患者口腔微生物群的α多样性低于健康对照,但各研究中细菌群落的研究结果并不一致。最佳证据综合法表明,有中等程度的证据支持口腔细菌与AD之间的总体关联,以及口腔细菌是AD的一个风险因素。
目前的证据适度支持口腔细菌与AD之间的关联,而当在大脑中检测到口腔细菌时,这种关联很强。需要进一步的证据来阐明单个物种和细菌群落与AD发展之间的相互关系。