Qing Xiangli, Zhang Chenhui, Zhong Zhuotai, Zhang Tao, Wang Lin, Fang Shuangshuang, Jiang Tianyuan, Luo Xiaoying, Yang Yang, Song Gengqing, Wei Wei
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Inflamm Bowel Dis. 2024 Aug 1;30(8):1251-1257. doi: 10.1093/ibd/izad188.
Periodontitis has been reported to be associated with inflammatory bowel disease (IBD), including ulcerative colitis (UC), and Crohn's disease (CD). However, the causality of these 2 diseases remains unclear. We conducted bidirectional Mendelian randomization (MR) to investigate the causal relationship between periodontitis and IBD.
We obtained the genome-wide association study (GWAS) summary data of European populations from FinnGen database (for IBD) and a published article (for periodontitis), from which independent single nucleotide polymorphisms were selected as instrumental variables. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for MR analysis. Heterogeneity or pleiotropy was detected through Cochran's Q test and MR-Egger intercept, respectively. Outlier was identified with MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) and leave-one-out analysis. All statistical analyses were performed with R 4.2.1 and the packages of TwoSampleMR version 0.5.6.
Genetic prediction showed that periodontitis was the risk factor of UC (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.26; P = .027), rather than of CD (OR, 0.92; 95% CI, 0.74-1.15; P = .456) and IBD (OR, 0.96; 95% CI, 0.81-1.13; P = .619). To the contrary, CD, not UC or IBD, resulted in exacerbating periodontitis in terms of the results of the IVW (OR, 1.09; 95% CI, 1.01-1.17; P = .021) and WM (OR, 1.10; 95% CI, 1.01-1.20; P = .030) methods. Heterogeneity or pleiotropy was acceptable.
Our results indicated that CD was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of UC, enhancing the existence of mouth-gut axis. Patients with UC should pay more attention to periodontal health, while patients with periodontitis should actively pay close heed to intestinal health.
据报道，牙周炎与炎症性肠病（IBD）有关，包括溃疡性结肠炎（UC）和克罗恩病（CD）。然而，这两种疾病之间的因果关系仍不清楚。我们进行了双向孟德尔随机化（MR）研究，以探讨牙周炎与IBD之间的因果关系。
我们从芬兰基因数据库（用于IBD）和一篇已发表的文章（用于牙周炎）中获取了欧洲人群的全基因组关联研究（GWAS）汇总数据，从中选择独立的单核苷酸多态性作为工具变量。采用逆方差加权（IVW）、MR-Egger和加权中位数（WM）方法进行MR分析。分别通过Cochran's Q检验和MR-Egger截距检测异质性或多效性。使用MR-PRESSO（孟德尔随机化多效性残差和异常值）和留一法分析识别异常值。所有统计分析均使用R 4.2.1和TwoSampleMR版本0.5.6的软件包进行。
遗传预测显示，牙周炎是UC的危险因素（优势比[OR]，1.13；95%置信区间[CI]，1.01-1.26；P = 0.027），而非CD（OR，0.92；95% CI，0.74-1.15；P = 0.456）和IBD（OR，0.96；95% CI，0.81-1.13；P = 0.619）的危险因素。相反，就IVW（OR，1.09；95% CI，1.01-1.17；P = 0.021）和WM（OR，1.10；95% CI，1.01-1.20；P = 0.030）方法的结果而言，是CD而非UC或IBD导致牙周炎加重。异质性或多效性是可接受的。
我们的结果表明，CD是牙周炎的危险因素；相反，牙周炎是UC病情加重的原因，这增强了口腔-肠道轴的存在。UC患者应更加关注牙周健康，而牙周炎患者应积极密切关注肠道健康。
