Periodontitis Role in Inflammatory Bowel Disease - PROJECT SUMMARY/ABSTRACT As opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomic, microbial, and immunologic ties that have bidirectional health implications. Our group has been at the forefront of unravelling the impact of oral health on intestinal health. Our recent clinical study highlighted a significant association between periodontitis, a prevalent oral infection, and inflammatory bowel disease (IBD), a chronic gastrointestinal disorder. IBD patients suffer from diarrhea, rectal bleeding, abdominal pain, and have a diminished quality of life, and shorter life expectancy. Between 1990 and 2017, the global incidence of IBD has surged by 31%, becoming a global health concern. To date, the etiology of IBD remains unclear, hindering the development of effective cures. The objective of this proposal is to elucidate the potential causal role of periodontitis in IBD using mechanistic studies in pre-clinical models, that serve as key investigative tools. Our preliminary data indicate that the concurrent presence of impaired intestinal barrier function and periodontitis increase the risk for intestinal inflammation. Based on this, our central hypothesis posits that in hosts with impaired intestinal barrier function, concurrent periodontitis enables certain oral pathogens to colonize the intestine and induce colonic inflammation. Our hypothesis will be tested using three Specific Aims that leverage animal models with intestinal barrier function disrupted by either genetic deficiency or medications. In Aim 1, we will determine if oral bacteria from IBD patients and ligature-induced periodontitis mice colonize the intestines to promote colonic inflammation. In Aim 2, we will elucidate the aberrant inflammatory responses activated by periodontitis and oral pathogens that mediate colonic inflammation. In Aim 3, we will identify the gastric acid resistance mechanisms of oral bacteria that enable them to overcome stomach acidity and colonize the gut, promoting colonic inflammation. Our rationale is that identification of pathways by which oral pathogens induce colonic inflammation will help in developing transformative oral-centric IBD therapies. The proposed research is significant because it will spur strategies to monitor oral health, optimize dental care, and target immune perturbations to reduce IBD risk in susceptible individuals.
