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J Autoimmun. 2016 Aug;72:47-56. doi: 10.1016/j.jaut.2016.05.001. Epub 2016 May 10.

Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice.

Author information

  • 1Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 2Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
  • 3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
  • 4Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: li.wen@yale.edu.

Abstract

Environmental factors clearly influence the pathogenesis of Type 1 diabetes, an autoimmune disease. We have studied gut microbiota as important environmental agents that could affect the initiation or progression of type 1 diabetes especially in the prenatal period. We used neomycin, targeting mainly Gram negative or vancomycin, targeting mainly Gram positive bacteria, to treat pregnant NOD mothers and to study autoimmune diabetes development in their offspring. Neomycin-treated offspring were protected from diabetes, while vancomycin-treated offspring had accelerated diabetes development, and both antibiotics caused distinctly different shifts in gut microbiota composition compared with the offspring from untreated control mice. Our study demonstrated that neomycin treatment of pregnant mothers leads to generation of immune-tolerogenic antigen-presenting cells (APCs) in the offspring and these APCs had reduced specific autoantigen-presenting function both in vitro and in vivo. Moreover, the protection from diabetes mediated by tolerogenic APCs was vertically transmissible to the second generation. In contrast, more diabetogenic inflammatory T cells were found in the lymphoid organs of the offspring from the vancomycin-treated pregnant mothers. This change however was not transmitted to the second generation. Our results suggested that prenatal exposure to antibiotic influenced gut bacterial composition at the earliest time point in life and is critical for consequent education of the immune system. As different bacteria can induce different immune responses, understanding these differences and how to generate self-tolerogenic APCs could be important for developing new therapy for type 1 diabetes.

KEYWORDS:

Antibiotic treatment; Gut microbiota; Type 1 diabetes

PMID:
27178773
PMCID:
PMC4958594
[Available on 2017-08-01]
DOI:
10.1016/j.jaut.2016.05.001
[PubMed - in process]
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