Oral Infections, Metabolic Inflammation, Genetics, and Cardiometabolic Diseases

Abstract

Although several epidemiologic studies reported plausible and potentially causal associations between oral infections and cardiometabolic diseases (CMDs), controversy still lingers. This might be due to unrecognized confounding from metabolic inflammation and genetics, both of which alter the immune responses of the host. Low-grade inflammation termed metainflammation is the hallmark of obesity, insulin resistance, type 2 diabetes, and CMDs. According to the common soil theory, the continuum of obesity to CMDs is the same pathology at different time points, and early metainflammations, such as hyperglycemia and obesity, display many adverse cardiometabolic characteristics. Consequently, adipose tissue is now considered a dynamic endocrine organ that expresses many proinflammatory cytokines such as TNF-α, IL-6, plasminogen activator inhibitor 1, and IL-1β. In metainflammation, IL-1β and reactive oxygen species are generated, and IL-1β is a pivotal molecule in the pathogenesis of CMDs. Note that the same cytokines expressed in metainflammation are also reported in oral infections. In metabolic inflammation and oral infections, the innate immune system is activated through pattern recognition receptors-which include transmembrane receptors such as toll-like receptors (TLRs), cytosolic receptors such as nucleotide-binding oligomerization domain-like receptors, and multiprotein complexes called inflammasome. In general, TLR-2s are presumed to recognize lipoteichoic acid of Gram-positive microbes-and TLR-4s, lipopolysaccharide of Gram-negative microbes-while nucleotide-binding oligomerization domain-like receptors detect both Gram-positive and Gram-negative peptidoglycans on the bacterial cell walls. However, a high-fat diet activates TLR-2s, and obesity activates TLR-4s and induces spontaneous increases in serum lipopolysaccharide levels (metabolic endotoxemia). Moreover, genetics controls lipid-related transcriptome and the differentiation of monocyte and macrophages. Additionally, genetics influences CMDs, and this creates a confounding relationship among oral infections, metainflammation, and genetics. Therefore, future studies must elucidate whether oral infections can increase the risk of CMDs independent of the aforementioned confounding factors.

Does Treatment of Periodontal Disease Influence Systemic Disease?

“…1) that has been called metainflammation. 168 It has the same negative consequences as any other inflammation and hence contributes to the total load of systemic inflammatory responses, which in turn affects all the inflammation-related diseases. Obesity, metabolic syndrome, type 2 diabetes, and CVD are part of a cardiovascularmetabolic dysfunction continuum that without sharp borders develop together.…”

Clinical and Translational Research

“…As of this writing, this month's clinical research supplement will be our final one, as we will now embark to collaborate with the new JDR Clinical & Translational Research editorial team on the publication of cutting-edge science in the area. In our final clinical research supplement, you will find some exciting advances in big data (DeRouen 2015), clinical bone augmentation strategies (Sanz et al 2015), cardiometabolic diseases (Janket et al 2015), and 3-dimensional printing (Obregon et al 2015), to name just a few.…”

Polymicrobial Biofilm Studies: from Basic Science to Biofilm Control

“…These findings were recapitulated using a murine model of P. gingivalis periodontal infection in which P. gingivalis could be recovered from the oral epithelium as well as aortal plaque demonstrating the in vivo tissue translocation potential of oral pathogens [74]. Despite these studies demonstrating a role for oral pathogens in the development of cardiac diseases more research will be required to determine whether periodontal disease is an independent risk factor for cardiac disease or is a result of underlying meta-inflammation, co-morbidities, or innate immunomodulation (for a review see Janket et al ., 2015) [75]. …”