Aims/hypothesis: Increasing evidence suggests that environmental
factors changing the normal colonisation pattern in
the gut strongly influence the risk of developing autoimmune
diabetes. The aim of this study was to investigate,
both during infancy and adulthood, whether treatment with
vancomycin, a glycopeptide antibiotic specifically directed
against Gram-positive bacteria, could influence immune
homeostasis and the development of diabetic symptoms in
the NOD mouse model for diabetes.

Methods: Accordingly, one group of mice received vancomycin
from birth until weaning (day 28), while another
group received vancomycin from 8 weeks of age until onset
of diabetes. Pyrosequencing of the gut microbiota and flow
cytometry of intestinal immune cells was used to investigate
the effect of vancomycin treatment.

Results: At the end of the study, the cumulative diabetes
incidence was found to be significantly lower for the neonatally
treated group compared with the untreated group,
whereas the insulitis score and blood glucose levels were
significantly lower for the mice treated as adults compared
with the other groups. Mucosal inflammation was investigated
by intracellular cytokine staining of the small intestinal
lymphocytes, which displayed an increase in cluster of
differentiation (CD)4+ T cells producing pro-inflammatory
cytokines in the neonatally treated mice. Furthermore, bacteriological
examination of the gut microbiota composition
by pyrosequencing revealed that vancomycin depleted many
major genera of Gram-positive and Gram-negative microbes
while, interestingly, one single species, Akkermansia muciniphila,
became dominant.

Conclusions/interpretation: The early postnatal period is a
critical time for microbial protection from type 1 diabetes
and it is suggested that the mucolytic bacterium A. muciniphila
plays a protective role in autoimmune diabetes development,
particularly during infancy.