Oral tolerance to foods can be regulated by microorganisms in the gut lumen. We hypothesized that pretreatment with avirulent Salmonella typhimurium strains could prevent food allergy in mice. Mice were administered S. typhimurium PhoPc (STPhoPc) or S. typhimurium AroA prior to oral sensitization to beta-lactoglobulin in the presence of cholera toxin. An oral antigen challenge after sensitization assessed antigen-induced anaphylaxis. Antigen-specific antibody titres were measured by enzyme-linked immunosorbent assay in the serum and enzyme-linked immunospot (ELISPOT) in the spleen, and cytokine-secreting cells were measured by ELISPOT in the Peyer's patches, lamina propria and epithelium cells. We showed first that S. typhimurium could up-regulate interleukin (IL)-12 and IL-10 secretion by gut T cells. Mice pretreated with STPhoPc had decreased anaphylaxis upon challenge, along with decreased immumoglobulin G1 (IgG1) and IgE antibody titres. Mice having received S. typhimurium AroA had partly decreased anaphylaxis as well as decreased serum IgG1 antibody titres in the serum, and increased serum IgA antibody titres. Antibody titres could be correlated with increased numbers of spleen and Peyer's patches antibody-producing cells. STPhoPc-treated mice showed significantly decreased anaphylaxis when compared with the control mice, while S. typhimurium AroA-pretreated mice had a similar immune response together with increased secretory IgA titres. Our experiments have proved a potential immunomodulatory protective effect by two avirulent S. typhimurium strains.