Zonulin as a Mediator of Psychological Stress and Periodontal Disease

Abstract

The prevalence of chronic inflammatory diseases is on the rise. Some have posited the permeability of tight junctions in gastrointestinal epithelium tissues as a potential mechanism for precipitating inflammatory processes throughout the body. Zonulin is the only known modulator of tight junction permeability and has been implicated in numerous chronic inflammatory processes (e.g., proinflammatory cytokine production) and diseases, more generally. The role of zonulin in oral inflammation, however, has yet to be explored. Periodontal disease is the most common oral inflammatory condition and primary perpetrator of tooth loss. Periodontal disease also is associated with a number of other health problems including heart disease and stroke and has previously been associated with psychological stress. The exact mechanisms between stress and inflammation, including in the periodontium, however, are less known. Thus, this dissertation was aimed at exploring whether moderate-to-severe periodontal disease was associated with higher levels of zonulin when compared to mild periodontal disease or otherwise healthy gingiva. Second, this study evaluated the mediating role of zonulin in helping to explain the relation between psychological stress and cytokines in participants with periodontal disease. Participants included 114 individuals (50.9% women, Mage = 36.1 years, SD = 14.0) from greater Morgantown, West Virginia who were part of a larger research project examining biobehavioral contributors to oral inflammation. Participants provided demographic and basic health information, a serum sample, underwent a periodontal examination, and filled out a battery of psychosocial questionnaires. Results indicated a potential relation between zonulin and periodontal disease status. In particular, zonulin was a significant predictor of number of teeth with probing depths of 5 millimeters or more in non-smoking individuals (β = 0.25, p = 0.029). Zonulin also was associated with indicators of more acute stages of periodontal inflammation, including the number of teeth with a probing depth of 5mm or more in a stepwise regression that included many common risk factors of periodontal disease. Additionally, dietary factors such as B-vitamins were associated with serum zonulin levels. Psychosocial variables, however, were not associated with zonulin or periodontal variables as anticipated. Other exploratory analyses were indicative of potential relations with depressive symptoms and zonulin, along with periodontal parameters. The results of this study provide preliminary implications for the role of zonulin and gastrointestinal distress in oral inflammation.