Year: 2024
Type: article
Study design: Observational Study
Abstract: Periodontitis (PD) potentiates systemic inflammatory diseases and fuels a feed-forward loop of pathogenic inflammation in obesity and type 2 diabetes (T2D). Published work in this area often conflates obesity with obesity-associated T2D; thus, it remains unclear whether PD similarly affects the inflammatory profiles of these 2 distinct systemic diseases. We collected peripheral blood mononuclear cells (PBMCs) from cross-sectionally recruited subjects to estimate the ability of PD to affect cytokine production in human obesity and/or T2D. We analyzed 2 major sources of systemic inflammation: T cells and myeloid cells. Bioplex quantitated cytokines secreted by PBMCs stimulated with T cell- or myeloid-targeting activators, and we combinatorially analyzed outcomes using partial least squares discriminant analysis. Our data show that PD significantly shifts peripheral T cell- and myeloid-generated inflammation in obesity. PD also changed myeloid- but not T cell-generated inflammation in T2D. T2D changed inflammation in samples from subjects with PD, and PD changed inflammation in samples from subjects with T2D, consistent with the bidirectional relationship of inflammation between these 2 conditions. PBMCs from T2D subjects with stage IV PD produced lower amounts of T cell and myeloid cytokines compared with PBMCs from T2D subjects with stage II to III PD. We conclude that PD and T2D affect systemic inflammation through overlapping but nonidentical mechanisms in obesity, indicating that characterizing both oral and metabolic status (beyond obesity) is critical for identifying mechanisms linking PD to systemic diseases such as obesity and T2D. The finding that stage IV PD cells generate fewer cytokines in T2D provides an explanation for the paradoxical findings that the immune system can appear activated or suppressed in PD, given that many studies do not report PD stage. Finally, our data indicate that a focus on multiple cellular sources of cytokines will be imperative to clinically address the systemic effects of PD in people with obesity.
Source: Journal of Dental Research
Institutions: University of Kentucky, The Forsyth Institute
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: bronze
Funders: University of Kentucky Research, National Institutes of Health, College of Dentistry, University of Kentucky, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences, Division of Diabetes, Endocrinology, and Metabolic Diseases
Awards: Inflammation in human obesity and type 2 diabetes, Roles for lymphocyte RANKL in periodontal complications of type 2 diabetes, G8467753105, Roles for lymphocyte RANKL in periodontal complications of type 2 diabetes, Diabetes Research Center, Restoration of Impaired Awareness of Hypoglycemia U01 Consortium: University of Kentucky, Kentucky Center for Clinical and Translational Science, OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository Core
OpenAlex ID: W4403258095