Abstract

In non-obese diabetic (NOD) mice, there is a sex-biased increase in female incidence of type 1 diabetes. Recently, the microbiome was found to protect male mice from type 1 diabetes. Transfer of microbiota from adult NOD male mice to pre-pubertal female mice protects against later incidence of sex-biased type 1 diabetes. This protection involves, in part, microbiome-mediated increased testosterone synthesis, which up-regulates the interleukin and interferon pathways. The microbiome-derived signals that mediate this response are unknown, although due to the diversity of chemicals synthesized in the microbiome some are likely to have structures unlike androgens. This suggests that novel synthetic and/or plant-derived chemicals may affect sex-biased autoimmune diseases through disruption of protective signaling networks between the microbiome and its host.

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