Authors: C H F Hansen L Krych D S Nielsen F K Vogensen L H Hansen S J Sørensen K Buschard A K Hansen
Publish Date: 2012/05/10
Volume: 55, Issue: 8, Pages: 2285-2294
Abstract
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 Grampositive bacteria could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetesAccordingly 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 treatmentAt 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 CD4+ T cells producing proinflammatory cytokines in the neonatally treated mice Furthermore bacteriological examination of the gut microbiota composition by pyrosequencing revealed that vancomycin depleted many major genera of Grampositive and Gramnegative microbes while interestingly one single species Akkermansia muciniphila became dominant
Keywords: