Periodontitis and Inflammatory Bowel Disease

A Meta-analysis

Yang-yang She; Xiang-bo Kong; Ya-ping Ge; Zhi-yong Liu; Jie-yu Chen; Jing-wei Jiang; Hong-bo Jiang; Si-lian Fang

Disclosures

BMC Oral Health. 2020;20(67) 

In This Article

Discussion

In the present meta-analysis, available evidence was summarized to help clarify the association of periodontitis and IBD. Overall, the results showed a positive association of periodontitis with IBD, CD and UC. According to the results, periodontitis was associated with a higher risk of IBD with low heterogeneity. Sensitivity analysis revealed the robustness of our results and the absence of publication bias added the validity of our results.

Accordingly, periodontitis may have an inverse relationship with IBD with different periodontal tissue destruction. Both CD and UC patients showed deeper pockets compared with the controls in the study of Brito, et al.[29] This is in contrast with Grossner-Schreiber, et al,[25] who found deeper pockets in the control group compared with patients with IBD. Most notably, the average CAL was the most important predictive factor for site progression. More sites with CAL were shown in patients with IBD than health controls by Brito, et al[29] and Grossner-Schreiber, et al,[25] which highlights the increased risk for periodontal tissue loss among these patients. However, varying extent of periodontal destruction was reflected in UC and CD patients. Compared with UC, CD patients were less vulnerable to CAL and developing sites with CAL ≥ 3 mm. This may indicate a potential difference in the pathophysiology of these two diseases, involving the T helper (Th) cell differentiation. UC is considered to be Th2 disease, while CD has characteristics of a Th1 disease. Another possible explanation for this difference might be due to patients with CD taking markedly more immunomodulators than those with UC.[29]

The observational studies on the the association between periodontitis and IBD are revealing, but it could be interfered by several confounding factors, such as gender, smoking, and medications. Thus, it is necessary to rely on properly adjusted risk estimates. One of the primary drivers of periodontitis is smoking, as proposed by the included studies. It has been shown that those who were ex-smokers and those who were having IBD were prevalent for periodontitis. In patients with CD, ex-smoking and clinical activity were significant risk factors for periodontitis.[27] But it seems to play a protective role in UC, with a decrease in the expression of proinflammatory Th1/Th17 cytokines in colon.[31] In addition, in IBD subgroups compared with healthy controls, the existence of perianal extraintestinal manifestations in IBD and proctitis in patients with UC were risk factors for periodontitis.[27] Furthermore, it is noteworthy that patients with IBD taking immunomodulators had a higher mean value of GI[30] and increased needs of periodontal treatment. The drug species applied to the treatment of IBD can lead to alterations on periodontal tissues due to the direct toxic effects, as well as indirect immunodepression effects with developing opportunistic infections.[32] However, in a retrospective cohort study, Chi, et al.[33] expounded an increased HR for subsequent periodontitis among CD patients when compared to matched controls, where treatment of CD showed protection against periodontitis due to the protective effect of some pharmaceuticals.

Although the etiology of IBD is still unclear, it has been hypothesized that IBD is mediated by chronic inflammation triggered by an environmental stimulus in a genetically primed individual.[9,20] Periodontitis is an inflammatory response caused by the stimulation of colonized Gram-negative bacteria.[9,20] Microbiological impact has been suggested as a potential factor accountable for the altered predisposition to periodontitis in IBD patients. Van Dyke et al.[34] reported a microflora composed of Gram-negative bacteria that was consistent with the genus Wolinell in a periodontal microflora of IBD patients. Brito et al.[15] showed that a high prevalence of Treponema denticola and other bacteria, in connection with opportunistic infections in subgingival sites, were found in IBD patients. The severity of periodontitis might be attributable to the crucial microbe-host interaction. Another linkage between periodontitis and IBD is related to immune-inflammatory response. Specifically, a possible role for G protein-coupled receptor 30 (GPR30) and tumor necrosis factor-α (TNF-α) has been implicated.[35–38] The level of TNF-α is elevated in the gastrointestinal tract of CD patients, as well as in the gingival crevicular fluid of periodontitis patients. GPR30 mRNA and protein expression were detectable in the colonic tissues of IBD patients and may play a role in the intestinal inflammatory balance.[36]

At present, our understanding of the mechanism that oral bacteria may contribute to the development of IBD is still evolving. When bacteria find a home in the dental plaque, local pro-inflammatory cytokines produced by the monocytes and macrophages activated by bacteria and their products might enter the systemic circulation.[39] Focusing on the oral bacteria, so as to initiating new ideas for the treatment of IBD. Treating both local oral and systemic inflammation would probably come under the spotlight for the optimal therapeutic strategies.

While a significant association was found between periodontitis and IBD, there were some limitations in this meta-analysis. First, all the studies included were English publications, leading to a possible language bias. Second, regional, ethnic, age, and diagnostic criteria for periodontitis may also be the sources of heterogeneity, but no further subgroup analysis was performed due to the limited number of studies and subjects. Third, not all six studies included here presented the adjusted estimates between periodontitis and IBD. As a result, potential confounding factors could lead to some bias in the association between periodontitis and IBD. Last but not least, the six studies included here were all case-control studies and no prospective large-scale cohort study has been published. The current data cannot be used to establish a cause-and-effect relationship between IBD and periodontitis. Further intervention studies are needed in order to establish such a causal relationship.

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