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.
Highlights
The human microbiome is in constant interaction with the host, modulating health and disease phenotypes
Based on our analysis the red complex pathogen, T. forsythia, was enriched in periodontitis subjects from Systemic lupus erythematosus (SLE)-active, but not in their healthy counterpart. In addition to these changes, we found S. noxia, S. oralis and A. gerencseriae at higher abundance in the SLE-I group compared with control individuals with periodontitis (Figure 2B, Figure 3A)
Oral microbes, including subgingival bacteria, are involved in homeostasis and maintenance of health, and in the initiation and progression of chronic periodontitis (CP) which leads to systemic inflammation such as SLE 41–47
Summary
The human microbiome is in constant interaction with the host, modulating health and disease phenotypes. Through local activation of inflammation, oral pathogens have shown to worsen the burden of chronic diseases through time including, type 2 diabetes, premature labor, rheumatoid arthritis, systemic lupus erythematosus (SLE), Alzheimer's, cardiovascular conditions, and cancer 1–4. Inflammation precedes tissue loss and the systemic impact of periodontal dysbiosis goes beyond the oral compartment. In addition to molecular diagnosis, systemic lupus erythematosus disease activity index (SLEDAI) is used in the assessment of disease severity and response to treatment; manifestations of comorbidities and molecular abnormalities affecting multiple organs of the body often challenges diagnostics at early stages 13. While several studies reported associations among human oral microbiota compositions in SLE 16–19, co-occurrences of specific periodontal pathogens and inflammatory cytokines important for low grade inflammation and chronic disease remains to be explored 4
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