Early Life Treatment With Vancomycin Propagates Akkermansia Muciniphila and Reduces Diabetes Incidence in the NOD Mouse

Diabetologia. 2012 Aug;55(8):2285-94. doi: 10.1007/s00125-012-2564-7. Epub 2012 May 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Flow Cytometry
  • Incidence
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mucins / metabolism
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Mucins
  • Vancomycin