Gut Microbiota in Lupus: a Butterfly Effect?

Purpose of Review Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that typically displays chronic inflammatory tissue damage and miscellaneous circulatory autoantibodies, as well as distinctive type 1 interferon signatures. The etiology of SLE is unclear and currently is attributed to genetic predisposition and environmental triggers. Gut microbiota has recently been considered a critical environmental pathogenic factor in immune-related disorders, and studies are ongoing to uncover the key pathogens and the imputative mechanisms. Fundamental advancements on the role of the microbiota in SLE pathology have been achieved in recent years and are summarized in this review. Recent Findings Recent findings suggested that gut commensals could propagate autoimmunity via molecular mimicry in which ortholog-carrying microbes cross-activate autoreactive T/B cells and trigger the response against host autoantigens, or via bystander activation by stimulating antigen-presenting cells that present autoantigens and enhancing the expression of co-stimulatory molecules and cytokines, thus leading to the loss of self-tolerance and the production of autoantibodies. Additionally, the break of gut barrier and the translocation of gut commensals to inner organs can trigger immune dysregulation and inappropriate systemic inflammation. All these microbiota-mediated mechanisms could contribute to lupus immunopathogenesis and promote disease development in susceptible individuals. Evidence of the causative role of disturbed gut microbiome in SLE is still limited, and the related molecular mechanisms and pathways are largely elusive. However, the modification of gut microbiota, such as pathobiont vaccine, special diet, restricted consortium transplantation, as well as regulatory metabolites supplementation, might be promising strategies for lupus prophylaxis and treatment.

Automated summary

Recent research has shown that gut microbiota play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Gut commensals may promote autoimmunity through molecular mimicry or bystander activation, leading to the loss of self-tolerance and production of autoantibodies. Disturbances in gut barrier and translocation of gut commensals to inner organs can trigger immune dysregulation and inappropriate systemic inflammation in SLE patients. Modifying gut microbiota, such as with pathobiont vaccines, special diets, restricted consortium transplantation, and regulatory metabolites supplementation, may be promising strategies for the prevention and treatment of lupus.