Gluten induces massive changes of mice gut microbiota composition that correlate with vaccine efficiency. mouse gut metagenome

Varying or even lack of efficiency of vaccines poses a major problem in ensuring public health. The efficiency of vaccines has been proposed to be influenced by genetic background, immune state and age but recently also gut microbiota composition has been suggested to influence vaccine efficiency. A rising number of studies support the link between gut microbiota and immune system development and functions. Furthermore, GM changes has been shown to be implicated in a number of immune system related disorders and diseases, such as obesity, diabetes, atherosclerosis, astma and allergy. The present study hypothesize that mice feed a diet containing gluten will develop an altered GM compared to mice fed a gluten free diet which in turn will influence immune system functions and change vaccine efficacy, in the present study a tetanus toxoid vaccine. Sixty three 7 weeks old BALB/c mice were randomized into 3 groups. One group was put on a gluten free diet and vaccinated after 1 and 3 weeks on the diet. The two other groups received a gluten containing diet, with one group being vaccinated as lined out above and one group serving as un-vaccinated control. Blood samples were collected and analysed for IgG titers and cytokine profiles. Faecal samples were collected and gut microbiota composition analysed using DGGE and 454/FLX-based high throughput sequencing. Interestingly diet were found to significantly influence IgG titers when determined after first vaccination, with the group on gluten containing diet showing on average higher and more uniform IgG titers compared to the group on gluten free diet, where the IgG titers on average were lower and varied widely between subjects. After the second vaccination no influence of diet were observed, with the 2 vaccinated groups showing comparable values. Principal component analysis revealed no significant differences in the GM profiles between the three groups of mice at arrival, but already after one week the GM separate significantly according to diet. Vaccination apparently had no influence on GM composition as evident when comparing the vaccinated and the non-vaccinated groups on gluten containing diet. METASTATS analysis of 454-reads showed that the abundance of 3 phyla were significantly different between the group receiving a gluten-containing diet compared to the group receiving a gluten free diet. At the genus level 20 taxonomic groups (15% of all registered taxonomic groups) were significantly different between the 2 diets. In conclusion the present study supports previous findings suggesting that gluten has the ability to alter the gut microbiota. Moreover, gluten seems to have the ability to influence the immune response initiated by tetanus toxoid vaccine, at primary vaccination. Whether the influence of gluten on the immune response is due to the alteration of gut microbiota, or via a direct alteration of the immune system remains to be fully elucidated.