Microbiota-derived short-chain fatty acids functions in the biology of B lymphocytes: From differentiation to antibody formation.

Gut bacteria produce various metabolites from dietary fiber, the most abundant of which are short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. Many biological functions, such as host metabolism and the immune system, are regulated by SCFAs because they act on a wide variety of cell types. A growing body of documents has shown that microbiota SCFAs directly regulate B-cell growth, proliferation, and immunoglobulin (Ig) production. As histone deacetylase (HDAC) inhibitors, SCFAs alter gene expression to enhance the expression of critical regulators of B cell growth. In particular, microbiota SCFAs increase the production of acetyl coenzyme A (acetyl-CoA), adenosine triphosphate (ATP), and fatty acids in B cells, which provide the energy and building blocks needed for the growth of plasma B cells. SCFAs play a significant role in promoting the involvement of B cells in host immunity during both homeostatic conditions and disease states. In this context, SCFAs stimulate B-cell activation and promote the differentiation of plasma B cells in response to B cell receptor (BCR)-activating antigens or co-stimulatory receptor ligands. The result may be increased production of IgA. Microbiota SCFAs were found to lower both overall and antigen-specific IgE levels, indicating their potential to mitigate IgE-related allergic reactions, much like their effect on class-switch recombination (CSR) towards IgG and IgA. Therefore, in the future, the therapeutic advantage should be to use specific and diffusible chemicals, such as SCFAs, which show a strong immunoregulatory function of B cells. This review focuses on the role of microbiota-produced SCFAs in regulating B cell development and antibody production, both in health and diseases.