Fig. 3
Shared and distinct effects of SCFAs on autoimmune diseases. While there are shared effects of SCFAs on most autoimmune diseases, the effects of SCFAs on the selected autoimmune diseases are heterogeneous. SCFA levels and microbiome diversity are decreased in most autoimmune diseases. Interestingly, SCFA levels are abnormally upregulated in a subset of lupus patients, indicating the presence of disease-specific dysbiosis and/or host metabolism in these subjects. SCFAs are known to activate B cells and induce AID expression to boost class-switched antibody production. Therefore, certain functions of SCFAs have the potential to exacerbate lupus and other autoimmune diseases. Common functions of SCFAs in promoting regulatory lymphocytes, such as Tregs and Bregs, and tolerant antigen-presenting cells appear to operate in most autoimmune diseases. Moreover, microbiota and SCFAs have the potential to shape the antigen receptor repertoire in developing lymphocytes. These functions would prevent autoimmunity in general and decrease ongoing autoimmune responses. In addition, SCFAs have metabolic effects, such as the induction of gut hormone (GLP-1 and PYY) secretion to decrease food intake and inflammatory responses, which could benefit both Type I and II diabetes patients. In contrast, the adverse effect of SCFAs on autoantibody production in lupus and other diseases is a potentially important problem. Despite the progress, it remains still unclear whether SCFAs have significant regulatory effects in many other autoimmune diseases. This is due to either a lack of information or contradictory functions of SCFAs in promoting both the effector and regulatory arms of the immune system
