Autoimmunity Mighty Male Microbes

Kristen L. Mueller

Science, AAAS, Washington, DC 20005, USA

Both genetic and environmental factors contribute to an individual’s susceptibility to autoimmune disease, but the specific environmental influences are not well characterized. Markle et al. (see the Perspective by Flak et al.) explored how microbial factors, in particular the gut microbiota, influence susceptibility to type 1 diabetes in mice. In the nonobese diabetic (NOD) mouse model of type 1 diabetes, female mice are significantly more susceptible to disease than males; however, this difference was not apparent under germ-free conditions. Transfer of cecal contents from male NOD mice to female NOD mice before disease onset protected against pancreatic islet inflammation, autoantibody production, and the development of diabetes and was associated with increased testosterone in female mice. Blocking androgen receptor activity abrogated protection. Thus, the microbiota may be able to regulate sex hormones and influence an individual’s susceptibility to autoimmunity.

J. G. M. Markle, D. N. Frank, S. Mortin-Toth, C. E. Robertson, L. M. Feazel, U. Rolle-Kampczyk, M. von Bergen, K. D. McCoy, A. J. Macpherson, J. S. Danska, Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 339, 1084–1088 (2013). [Abstract] [Full Text]

M. B. Flak, J. F. Neves, R. S. Blumberg, Welcome to the microgenderome. Science 339, 1044–1045 (2013). [Summary] [Full Text]

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