Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis

Abstract

Systemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche to assay local dynamic microbial ecological changes in health and disease important to systemic inflammation in SLE subjects. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiota on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy (n=31), SLE-inactive (n=29), and SLE-active (n=31). Patients were screened for probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and classified with or without periodontal dysbiosis, periodontitis. Serum inflammatory cytokines were measured by human cytokine panel and subgingival biofilm was examined by DNA-DNA checkerboard. The results showed significant upregulation of proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject's into SLEinactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. While low-grade inflammation was found in SLE-Isubjects, a potent anti-inflammatory cytokine, IL-10 was found to control clinical phenotypes. Out of twenty-four significant differential oral microbial abundances found in SLE, fourteen unique subgingival bacteria profiles were found to be elevated in SLE. Pathogens from periodontal disease sites (Treponema denticola and Tannerella forsythia) showed increase abundance in SLE-A subjects when compared to controls. Cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Deeper 2 clinical attachment loss and periodontal pathogens were found in SLE subjects, especially on SLE-I, likely due to long-term chronic and low-grade inflammation. Altogether, local periodontal pathogen enrichment was positively associated with high systemic inflammatory profiles, relevant to the overall health and SLE disease pathogenesis.

Transcriptomics of Type 2 Diabetic and Healthy Human Neutrophils

“…The 20 assayed cytokines were: MIP-1α, IL-1β, IL-4, IP-10, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ, GM-CSF, TNF-α, MIP-1β, IFN-α, MCP-1, P-Selectin, IL-1α, sICAM-1, and E-Selectin. Following manufacturer protocols, all samples were run on a plate with 7 standards (diluted 1:4) and a control (RPMI only), with all samples, standards, and controls run in duplicate (19).…”

Periodontitis, Low-Grade Inflammation and Systemic Health: A Scoping Review

“…Pessoa et al [ 42 ] evaluated the reciprocal impact of periodontal subgingival microbiome on systemic lupus erythematosus and systemic inflammation. Circulating proinflammatory cytokines were upregulated in patients with SLE, inducing an LGI status.…”

“…The systemic LGI status seems to be influenced by the composition of the oral microbiome [ 42 ], which changes as a consequence of periodontitis so that higher levels of circulating inflammatory markers have been described in periodontal patients compared to healthy subjects [ 46 , 50 , 51 , 52 , 53 ].…”

Periodontitis and Systemic Lupus Erythematosus: A systematic review and meta‐analysis

“…The majority of the observational studies included in this review presented with a moderate risk of bias 2,3,25–35 , one with high 36 and three with low risk of bias 37–39 (Supplementary , Appendix , Table ). Among the main factors behind study bias we have identified: definition adequacy, representativeness of the cases, selection and definition of the controls, representativeness of exposed cohort and demonstration that outcome of interest was not present at start of study.…”