This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The oral cavity provides a biotope for many bacterial species, which may be considered commensal, opportunistic or pathogenic. The host defense systems are important for monitoring the composition of the bacterial microbiota and preventing disease initiation and progression. Innate and adaptive immune mechanisms serve to prevent inappropriate responses to commensal microbes, regulate opportunistic species, and sequester pathogens. Dysregulation of these responses can lead to chronic inflammatory conditions in the oral cavity, i.e., gingivitis and periodontitis. Understanding the molecular signaling mechanisms that maintain homeostasis in the oral cavity is key to understanding the pathology of diseases in response to oral bacteria. Host cells respond to microorganisms through pattern recognition receptors (PRRs) such as Toll-like Receptors (TLRs), which recognize broad classes of pathogen associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), lipopeptides and microbial nucleic acids. Inflammatory bowel diseases (Crohn's and Ulcerative colitis) are chronic conditions that reflect an altered communication between resident gut flora and both the innate and acquired immune arms. The initiating factor is unknown, but lately a primary epithelial defect has been favored. A significant number of patients with inflammatory bowel diseases develop oral lesions but the incidence of periodontitis has not been adequately established. Patients with IBD (inflammatory bowel diseases) represent a heterogeneous group, more so when expression of individual genes within the gut mucosa is analyzed. We have recently identified unique subgroups of patients with Crohn's disease based on expression of biomarkers for innate immunity in the colonic mucosa. Additionally we have uncovered strong associations with a fat derived anti-inflammatory adipokine, adiponectin. The current proposal investigates the association between periodontitis and Crohn's disease and the relevance of disease specific biomarkers for this oral chronic inflammatory condition, using a GENERAL HYPOTHESIS that patients with IBD have a greater risk for periodontitis due to an underlying defect in innate immune responses at mucosal surfaces. IBD refers to idiopathic inflammatory diseases of the intestine, principally ulcerative colitis and Crohn's disease. There is no cure for IBD and the current medical management of IBD consists of anti-inflammatory and immunosuppressive agents. Evidence supporting inflammatory dysregulation as a critical factor in the pathogenesis of IBD and periodontitis has suggested potential underlying relationships in host response characteristics to their autochthonous microbiota in triggering these chronic inflammatory diseases.
Specific Aim 1. Determine the prevalence of periodontitis in patients with chronic inflammatory bowel conditions. This includes subsets of patients with Crohn's disease, Ulcerative Colitis, and Celiac Sprue. Additionally, a prospective assessment of periodontitis presentation in IBD patients receiving immunosuppressive treatment or following introduction of a gluten free diet will be performed. Finally, we will examine the likely effect of environmental (smoking) and nutritional (obesity) factors on IBD and periodontitis.
Specific Aim 2. Correlate validated Inflammatory Bowel Disease signature biomarkers in both the oral and intestinal mucosa. These studies will validate the biomarkers of IBD in periodontitis patients with/without IBD. We are also evaluating the relevance of adiponectin receptor expression and salivary high molecular weight (HMW) adiponectin in patients with periodontitis with/without IBD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR020145-08
Application #
8360731
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
2011-08-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
8
Fiscal Year
2011
Total Cost
$239,573
Indirect Cost
Name
University of Kentucky
Department
Dentistry
Type
Schools of Dentistry
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Lyons, Danielle N; Zhang, Liping; Danaher, Robert J et al. (2017) PPAR? Agonists Attenuate Trigeminal Neuropathic Pain. Clin J Pain 33:1071-1080
Danaher, Robert J; Fouts, Derrick E; Chan, Agnes P et al. (2017) HSV-1 clinical isolates with unique in vivo and in vitro phenotypes and insight into genomic differences. J Neurovirol 23:171-185
Gonzalez, O A; Kirakodu, S; Novak, M J et al. (2017) Comparative analysis of microbial sensing molecules in mucosal tissues with aging. Immunobiology :
Nagarajan, R; Miller, C S; Dawson 3rd, D et al. (2017) Cross-talk between clinical and host-response parameters of periodontitis in smokers. J Periodontal Res 52:342-352
Ebersole, J L; Kryscio, R J; Campbell, C et al. (2017) Salivary and serum adiponectin and C-reactive protein levels in acute myocardial infarction related to body mass index and oral health. J Periodontal Res 52:419-427
Nagarajan, Radhakrishnan; Al-Sabbagh, Mohanad; Dawson 3rd, Dolph et al. (2017) Integrated biomarker profiling of smokers with periodontitis. J Clin Periodontol 44:238-246
Huang, Chifu B; Alimova, Yelena; Ebersole, Jeffrey L (2016) Macrophage polarization in response to oral commensals and pathogens. Pathog Dis 74:
Gonzalez, Octavio A; Orraca, Luis; Kensler, Terry B et al. (2016) Familial periodontal disease in the Cayo Santiago rhesus macaques. Am J Primatol 78:143-51
Johnson, N; Ebersole, J L; Kryscio, R J et al. (2016) Rapid assessment of salivary MMP-8 and periodontal disease using lateral flow immunoassay. Oral Dis 22:681-7
Ma, Fei; Wang, Chunmei; Yoder, William E et al. (2016) Efficacy of Herpes Simplex Virus Vector Encoding the Human Preproenkephalin Gene for Treatment of Facial Pain in Mice. J Oral Facial Pain Headache 30:42-50

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