Abstract Immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation (SHM), as initiated by AID, and plasma cell differentiation, as mediated by Blimp-1, are critical for the maturation of the antibody response. This, as we have suggested, can be modulated by epigenetic modifications arising from environmental factors, such as the gut microbiota. Here we show that the gut microbiota regulates host immune responses through the production of metabolites such as short chain fatty acids (SCFAs). Butyrate and propionate are two of the major metabolic products generated by gut microbiota through processing of dietary fibers. They effectively dampened local and systemic IgG, IgA and IgE responses through B cell-intrinsic modulation of Aicda and Prdm1 gene expression, and, therefore, CSR/SHM and plasma cell differentiation. This SCFA-mediated reduction of class-switched B cells and plasma cells in PP, MLNs and the spleen curtailed the antibody response to T-dependent and T-independent antigens. It also virtually abrogated the allergic IgE responses to house dust mite and peanut as well as the lupus IgG autoantibody response. Mice fed fiber-free diets showed reduced levels of gut SCFAs and increased titers of serum IgG, IgA, and IgE, which were reversed by the administration of exogenous butyrate and propionate. SCFA-mediated modulation of B cell was not due to their G-protein coupled receptor signaling or their use as an energy source. Rather, it resulted from their HDAC inhibitory activity, which upregulated select miRNAs silencing Aicda and Prdm1 mRNAs. Thus, the gut microbiota modulates B cell differentiation and antibody responses through B cell-intrinsic epigenetic regulation, by fiber processing metabolic products.