Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis

Abstract

Background: 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 for local and systemic inflammation. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiome on SLE systemic inflammation.Methods: 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, bleeding on probing, clinical attachment level, and classified according to CDC/AAP criteria with or without periodontal dysbiosis. Serum inflammatory cytokines were measured by human cytokine panel and a targeted pathogenic subgingival biofilm panel was examined by DNA-DNA checkerboard from subgingival plaque samples.Results: The results showed significant upregulation of serum proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject's into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. Ten proinflammatory cytokines were upregulated in serum of SLE-I only and one in SLE-A only. Four molecules overlapped in SLE-A and SLE-I. Anti-inflammatory cytokines included IL-4 IL-10, which were upregulated in SLE-I sera (but not SLE-A), controlling clinical phenotypes. Out of 24 significant differential oral microbial abundances found in SLE, 14 unique subgingival bacteria profiles were found to be elevated in SLE. The most severe oral pathogens (Treponema denticola and Tannerella forsythia) showed increase abundances on SLE-A periodontal sites when compared to SLE-I and healthy controls. Inflammation as measured by cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically.Conclusions: Altogether, low-grade systemic inflammation that influenced SLE disease activity and severity was correlated to dysbiotic changes of the oral microbiota present in periodontal diseases.

Longitudinal Study of Oral Microbiome Variation in Twins

“…Our findings indicate that the host environment drives changes in the oral microbiome over time. Consistently with our study on supra-gingival plaque, salivary microbial abundance was also influenced by the environment and host phenotypes 27 . While the biofilm is directly correlated to demineralization of enamel, saliva provides the source of microbes which through evolution adapted to attach to the tooth surface.…”

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).…”

Association between periodontitis and systemic lupus erythematosus: a meta-analysis

“…10 In addition, a recent study showed that the inflammatory response in periodontitis controls not only SLE severity, but also the magnitude of SLE disease. 11 Moreover, another clinical investigation showed that periodontal treatment appears to improve the response of SLE to immunosuppressive therapy. Therefore, further elucidation of the association between periodontitis and SLE could help to expand understanding of the aetiology of SLE and may lead to novel prevention and treatment strategies.…”