Oral Dysbiosis and Autoimmunity: From Local Periodontal Responses to an Imbalanced Systemic Immunity. A Review

Abstract

The current paradigm of onset and progression of periodontitis includes oral dysbiosis directed by inflammophilic bacteria, leading to altered resolution of inflammation and lack of regulation of the inflammatory responses. In the construction of explanatory models of the etiopathogenesis of periodontal disease, autoimmune mechanisms were among the first to be explored and historically, for more than five decades, they have been described in an isolated manner as part of the tissue damage process observed in periodontitis, however direct participation of these mechanisms in the tissue damage is still controversial. Autoimmunity is affected by genetic and environmental factors, leading to an imbalance between the effector and regulatory responses, mostly associated with failed resolution mechanisms. However, dysbiosis/infection and chronic inflammation could trigger autoimmunity by several mechanisms including bystander activation, dysregulation of toll-like receptors, amplification of autoimmunity by cytokines, epitope spreading, autoantigens complementarity, autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, and activation or inhibition of receptors related to autoimmunity by microorganisms. Even though autoreactivity in periodontitis is biologically plausible, the associated mechanisms could be related to non-pathologic responses which could even explain non-recognized physiological functions. In this review we shall discuss from a descriptive point of view, the autoimmune mechanisms related to periodontitis physio-pathogenesis and the participation of oral dysbiosis on local periodontal autoimmune responses as well as on different systemic inflammatory diseases.

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic

“…The role of the human microbiota in autoimmune diseases has attracted increased attention ( 24 ). However, how the oral microbiota affects PBC is not fully understood.…”

Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis

“…Recent studies have shown an association between IL17 and many inflammatory and autoimmune diseases such as systemic lupus erythematosus, sclerosis multiple, asthma and inflammatory bowel disease (IBD) ( 112 ). Alternatively, tolerogenic DCs can eliminate or block T cells, resulting in resolution of ongoing immune responses and prevention of autoimmune responses, which despite having been reported as widely prevalent in oral mucosa, seem to be related to non-pathologic responses and even represent non-recognized physiological functions as the immune removal of debris ( 115 , 116 ). Alternatively, tolerogenic DCs can eliminate or block T cells, resulting in resolution of ongoing immune responses and prevention of autoimmunity ( 115 ).…”

Systemic Lupus Erythematosus and Periodontal Disease: A Complex Clinical and Biological Interplay

“…Besides genetics, epigenetic modifications as a result of the interaction of bacterial metabolites and epigenetic enzymatic reactions, are also involved in pathogenesis of both PD and SLE [ 48 ]. Epigenetic mechanisms, such as DNA methylation and histone modification can trigger breakdown of immunological homeostasis of periodontal environment, but further investigations are needed to a more complete understanding of cyclic inflammation/dysbiosis process.…”

“…Potential mechanisms linking the SLE with the pathogenesis of PD include (i) the effects of systemic immune dysregulation on subgingival microbiota; (ii) the SLE-induced imbalance between pro-inflammatory and anti-inflammatory cytokines, which seems to be the cause of tissue damage [ 36 ]; (iii) the activation of autoreactive B cells and dysregulation of several other immune cell types, including macrophages, neutrophils, CD4+ T cells, and dendritic cells [ 48 ].…”