The Role of the Oral Spirochete Treponema Denticola in Periodontitis and Orodigestive Carcinogenesis
Year: 2018
Type: dissertation
Study design: Observational Study
Abstract: Periodontitis is an inflammatory disease of the tooth supporting tissue, including gingiva, bone and periodontal ligament structures. Chronic periodontitis is highly prevalent in adult population and it has been linked to various systemic diseases, such as cardiovascular diseases. Certain members of the oral microbiome, the so called periodontopathogens play a major role in its pathophysiology. Chronic inflammatory conditions can be considered to be predisposing factors for cancer. Periodontitis have been associated with elevated oral and gastrointestinal cancer risk and mortality. However, the mechanisms are still largely unknown. Periodontopathogen and spirochete Treponema denticola (T. denticola) possesses plethora of enzymes, such as chymotrypsin-like protease (CTLP), that facilitate its invasion into adjacent tissues and integration into microbial communities. The first study investigated the role of T. denticola in chronic periodontal inflammation. The study focused on evaluating T. denticola–induced cell death and associated danger signals and key inflammatory cytokines. The analysis compared the occurrence of these factors in patients with either gingivitis, periodontitis or in health using immunostaining approaches. In the second study, the presence of CTLP was evaluated in various oral and gastrointestinal cancers, including oral, tonsillar, esophageal, gastric, pancreatic and colon cancer. In addition, the presence of CTLP in the non- digestive tract cancer tissues including lung, breast and thyroid were analysed. The immunomodulatory actions of CTLP were investigated under laboratory conditions. In third study, CTLP was compared to several major clinical parameters such as depth of invasion and cancer size. The tissue analyses were carried out using immunohistochemistry. The results show that T. denticola induces and contributes to apoptosis via endogenous danger signals released from the late apoptotic cells.T. denticola CTLP was found in several cancer tissues in the orodigestive tract, but not in non-digestive tract cancer tissues. CTLP was able to activate key immunomodulatory mediators for tumor microenvironment such as pro-matrix metalloproteinases (proMMPs). The presence of CTLP in tongue cancer correlates with a number of key clinical aspects such as the degree of tumor invasion and size. In addition, high immunopositivity of CTLP was associated with the early cancer relapse in tongue cancer patients. This study helps to understand the mechanisms underlying T. denticola induced chronic inflammation in periodontal tissues. In addition, the study shows that the key virulence factor of T. denticola CTLP is present in multiple different orodigestive cancers. The results also elucidate potential actions CTLP possess in cancer microenvironment. These findings underline the fact that prevention and early diagnosis of periodontitis is not only vital for the oral but also for the general health.
Source: Työväentutkimus Vuosikirja
Author: Dyah Listyarifah
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2895159502