Unraveling the Link between Periodontitis and Inflammatory Bowel Disease: Challenges and Outlook

Periodontitis and Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions, characterized by microbial dysbiosis and hyper-immunoinflammatory responses. Growing evidence suggest an interconnection between periodontitis and IBD, implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an Oral-Gut axis, marked by a higher prevalence of periodontitis in IBD patients and vice versa. The specific mechanisms linking periodontitis and IBD remain to be fully elucidated, but emerging evidence points to the ectopic colonization of the gut by oral bacteria, which promote intestinal inflammation by activating host immune responses. This review presents an in-depth examination of the interconnection between periodontitis and IBD, highlighting the shared microbiological and immunological pathways, and proposing a multi-hit hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.Comment: Total Words: 7,016 Figures: 3 Tables: 2 Reference: 34

Bisphosphonate-related osteonecrosis of the jaw

University of Minnesota Ph.D. dissertation. May 2013. Major: Oral Biology. Advisor: Rajaram Gopalakrishnan. 1 computer file (PDF); vii, 185 pages.Bisphosphonates (BP), potent osteoclast inhibitors, play a key role in managing patients with osteoporosis, Paget’s disease, bone metastasis, and multiple myeloma. BP’s anti-resorptive activity substantially reduce fracture risk by 40%-70% in osteoporosis patients, and improve quality of life in cancer patients by preventing skeletal complications. However, prolonged BP use is associated with a significant dental complication termed “Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)”. To date, the true incidence, etiology, and risk factors that contribute to BRONJ pathogenesis are unknown. In this dissertation, we assessed the frequency, etiology and risk factors that contribute to BRONJ pathogenesis. We noted that the BRONJ frequency in cancer patients is around 3.1%. Factors such as poor periodontal status, diabetes, smoking, prolonged duration of BP therapy, and higher numbers of BP infusions significantly increase the risk of developing BRONJ. In addition, long-term BP administration adversely affects jawbone mechanical properties that could result in increased microdamage accumulation within the jaw bones. Furthermore, using proteomic analysis we identified 200 salivary proteins that were differentially expressed in BRONJ subjects. A majority of the differentially expressed proteins were predicted to have a role in dermatological diseases, genetic disorders, immunological diseases, and inflammatory responses. Finally, analysis of serum samples revealed that VEGF levels are significantly suppressed in patients undergoing BP therapy. In summary, results from this dissertation provide insight into the pathogenesis of BRONJ development.Thumbigere Math, Vivek. (2013). Bisphosphonate-related osteonecrosis of the jaw. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/154579

Baltimore oral epidemiology, disease effects, and HIV evaluation study (BEEHIVE) study protocol: a prospective cohort study

Abstract Background As antiretroviral therapy has become widely available and highly effective, HIV has evolved to a manageable, chronic disease. Despite this health advancement, people living with HIV (PLWH) are at an increased risk for age-related non-communicable diseases (NCDs) compared to HIV-uninfected individuals. Similarly, PLWH are at an increased risk for selected oral diseases. PLWH with a history of injecting drugs experience an even greater burden of disease than their counterparts. The overall objective of the Baltimore Oral Epidemiology, Disease Effects, and HIV Evaluation (BEEHIVE) study is to determine the combined effects of HIV infection and NCDs on oral health status. The specific aims of the study are to: (1) determine to what extent HIV status influences access to and utilization of oral health care services; (2) determine to what extent HIV status affects self-reported and clinical oral health status; (3) determine to what extent HIV status influences the progression of periodontitis; and (4) determine to what extent HIV status impacts the periodontitis-associated oral microbiome signature. Methods The BEEHIVE study uses a prospective cohort study design to collect data from participants at baseline and at a 24-month follow-up visit. Data are collected through questionnaire assessments, clinical examinations, and evaluation of oral microbiological samples to determine the drivers of oral disease among a high-risk population of PLWH with a history of injection drug use and prevalent comorbid NCDs. The established AIDS Linked to the Intravenous Experience (ALIVE) cohort serves as the source of participants for the BEEHIVE Study. Discussion Upon completion of the BEEHIVE study, the knowledge gained will be important in informing future clinical and preventive interventions that can be implemented into medical and dental practice to ultimately help eliminate long-standing oral health inequities that PLWH experience

M2a macrophages facilitate resolution of chemically-induced colitis in TLR4-SNP mice

ABSTRACT Toll-like receptor 4 (TLR4) is an innate immune receptor responsive to lipopolysaccharide (LPS). Single nucleotide polymorphisms (SNPs) in human TLR4 that encode an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I) render individuals hyporesponsive to LPS. In humans, these SNPs are also associated with increased susceptibility to inflammatory bowel diseases (IBDs). Using knock-in mice engineered to express the murine homologs of these human TLR4 mutations (“TLR4-SNP” mice), we have shown that TLR4-SNP mice develop significantly more severe colitis induced by dextran sodium sulfate (DSS) than wild-type (WT) mice, similar to IBD in humans expressing these SNPs. Previous studies have provided indirect evidence for “tissue repair” M2 macrophages (Mφ) in the resolution of colitis. Signaling through the IL-4/IL-13 receptor, IL-4Rα, and the transcription factor, peroxisome proliferator-activated receptor (PPARγ), have been shown to be required for induction of M2a Mφ, and our data provide direct evidence for the involvement of both in the repair of DSS-induced colonic damage. In response to DSS, colons of TLR4-SNP mice produced reduced levels of M2a Mφ marker mRNA and protein, including PPARγ, and therapeutic administration of the PPARγ agonist ligand, rosiglitazone, resolved colitis in TLR4-SNP mice, and increased expression of the M2a protein, Ym1. Together, these data indicate that the failure of TLR4-SNP mice to resolve DSS-induced colitis may be secondary to their failure to induce “tissue repair” M2a Mφ. Importance Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, impacts millions of individuals worldwide and severely impairs the quality of life for patients. Dysregulation of innate immune signaling pathways reduces barrier function and exacerbates disease progression. Macrophage (Mφ) signaling pathways are potential targets for IBD therapies. While multiple treatments are available for IBD, (i) not all patients respond, (ii) responses may diminish over time, and (iii) treatments often have undesirable side effects. Genetic studies have shown that the inheritance of two co-segregating SNPs expressed in the innate immune receptor, TLR4, is associated with human IBD. Mice expressing homologous SNPs (“TLR4-SNP” mice) exhibited more severe colitis than WT mice in a DSS-induced colonic inflammation/repair model. We identified a critical role for M2a “tissue repair” Mφ in the resolution of colitis. Our findings provide insight into potential development of novel therapies targeting Mφ signaling pathways that aim to alleviate the debilitating symptoms experienced by individuals with IBD