Study Characteristics The literature search process is summarized in Figure 1. risk of periodontitis was significantly higher in IBD patients than controls (OR: 2.10, 95% CI: 1.60-2.74; value 0.05 was considered statistically significant. 3. Results 3.1. Study Characteristics The literature search process is summarized in Figure 1. Briefly, 467 articles were retrieved by an initial database search, including exclusion of duplications. Four hundred and fifty-nine publications were excluded after screening the abstracts. Two relevant publications were excluded because they did not include the prevalence of periodontitis as a separate observation [7, 22]. Finally, a total of 6 publications were pooled for analysis with a total of 3711 patients [11, 12, 14, 23C25]. The included studies were VU 0240551 published between 2004 and 2020, reporting data from VU 0240551 Greece, Germany, Brazil, Sweden, Jordan, and China. The characteristics of these studies are shown in Table 2. Open in a separate window Figure 1 Flow chart demonstrating the study selection process. VU 0240551 Table 2 Characteristics of the included studies. 0.001). Open in a separate window Figure 3 Forest plot demonstrating the association between the risk of periodontitis and CD ( 0.001). Open in a separate VU 0240551 window Figure 4 Forest plot demonstrating the association between the risk of periodontitis and UC (= 0.0145). 3.4. Sensitivity Analysis Heterogeneity analysis showed that the = 0.23 for IBD vs. = 0.42 for CD and 0.01 for UC). The potential effects of any single study on heterogeneity were investigated by sensitivity analysis. Briefly, each study was removed sequentially to obtain the OR. When analyzing the remaining studies, we found that the heterogeneity across studies significantly decreased after removing the study by Zhang et al. [25] (= 0.16), suggesting it was the source of the heterogeneity. The OR of periodontitis for UC after exclusion of the Zhang et al. study was 1.71 (95% CI: 1.07-2.73; = 0.0239). 4. Discussion In recent decades, the association between IBD and periodontitis has been recognized on account of their similar etiologies. Both diseases involve dysbiotic microbiota, deregulation of the immune response, and chronic inflammation in genetically susceptible individuals [26C28]. Our study found that IBD patients had a higher risk of periodontitis than controls (OR: 2.10, 95% CI: 1.60-2.74; and IL-6 correlate with specific oral lesions [44]. TNF inhibitors have been used to treat IBD and could reduce inflammation and stop disease progression [45]. Similarly, anti-TNF treatment has shown promising results in periodontitis. In periodontitis animal models, anti-TNF treatment can reduce inflammatory cell recruitment and bone loss [46, 47]. This evidence indicates that IBD and periodontitis share similar immunological etiologies. Despite their similar etiologies, it is likely that IBD and periodontitis could trigger one another. That is, periodontitis, as one of the extraintestinal manifestations of IBD, could present before or after the onset of intestinal symptoms. There were limited studies that evaluated the risk of IBD in patients with periodontitis [48, 49]. A cohort study reported VU 0240551 a 1.56-fold significantly higher risk of UC, but not CD, in patients with periodontal disease [48]. Similarly, it was found that the risk of developing UC increased significantly in patients with periodontitis in a recent retrospective study involving 1 million subjects [49]. In this PPP1R60 meta-analysis, it was found that patients with UC had a higher risk for developing periodontitis than CD patients (OR:2.39 vs. OR: 1.72). This evidence suggests periodontitis is more correlated with UC than with CD. Certain limitations must be considered when interpreting the results of this study. First, there were some differences in the definition of periodontitis in the included studies, which may have caused some bias. Furthermore, the use of studies including self-reported periodontitis could have introduced measurement error. The risk of developing periodontitis in IBD subjects may be higher in fact. Second, the risk of developing periodontitis among patients with IBD was not adjusted for relevant factors, especially medications and smoking habits. The use of antibiotics, immunomodulatory drugs, and corticosteroids are possible confounders for evaluating the risk of periodontitis in IBD patients. Smoking is a risk for periodontitis [50], whereas individuals who smoke have a.