Effect of gluten-free diet and antibiotics on murine gut microbiota and immune response to tetanus vaccination

by Pernille Kihl, Lukasz Krych, Ling Deng, Lars H. Hansen, Karsten Buschard, Søren Skov, Dennis S. Nielsen, Axel Kornerup Hansen

The purpose of this study was to compare the effect of a gluten-free diet and/or antibiotics on tetanus vaccine induced immunoglobulin G titers and immune cell levels in BALB/c mice. The gluten-free diet was associated with a reduced anti-tetanus IgG response, and it increased the relative abundance of the anti-inflammatory Bifidobacterium significantly in some of the mice. Antibiotics also led to gut microbiota changes and lower initial vaccine titer. After a second vaccination, neither gluten-free diet nor antibiotics reduced the titers. In the spleen, the gluten-free diet significantly increased regulatory T cell (T_reg) fractions, CD4⁺ T cell activation, and tolerogenic dendritic cell fractions and activation, which extend the downregulating effect of the T_reg. Therefore, the systemic effect of the gluten-free diet seems mainly tolerogenic. Antibiotics reduced the fractions of CD4⁺ T and B cells in the mesenteric lymph nodes. These results suggest that vaccine response in mice is under influence of their diet, the gut microbiota and the interplay between them. However, a gluten-free diet seems to work through mechanisms different from those induced by antibiotics. Therefore, diet should be considered when testing vaccines in mice and developing vaccines for humans.