Vancomycin treated NOD mice

Establishment of an intestinal microbial ecosystem during infancy is a major drive for postnatal development of the immune system. It has been suggested that environmental factors changing the normal colonization pattern play an essential role in the risk of developing autoimmune diseases. The aim of this study was to investigate whether vancomycin treatment, both during infancy and adulthood, could influence immune homeostasis and diabetes development in the spontaneously diabetic NOD mouse model. Accordingly, one group received vancomycin only during the first four weeks of life and another group received vancomycin from eight weeks of age and until they were diagnosed diabetic. Both groups were compared to a control group and sampled upon euthanization for bacteriological and immunological examinations. The cumulative diabetes incidences were lower for both treated groups but only significant for the neonatal treated group. In addition, intestinal immune analyses of only neonatal treated mice revealed a pro-inflammatory signature while the immune-regulatory status remained unchanged. Vancomycin treated mice had significantly higher numbers of Verrucomicrobium and Proteobacteria at the expense of both Firmicutes and Bacteroidetes. The results are highly indicative of an anti-diabetic effect of a less gram positive flora in early life. Differences in gut flora composition were primarily due to a mani-fold increase in Akkermansia muciniphila during vancomycin treatment and it is likely to assume that this mucolytic bacterium play a protective role in diabetes development.