Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity
Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity
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DOI：
10.1126/science.1233521
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发表时间：
2013-03-01
期刊：
影响因子：
56.9
通讯作者：
Danska, Jayne S.
中科院分区：
文献类型：
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作者：
Markle, Janet G. M.;Frank, Daniel N.;Danska, Jayne S.
微生物暴露和性激素对自身免疫性疾病产生强有力的影响，其中许多在女性中更为普遍。我们证明，在1型糖尿病（T1D）的非肥胖糖尿病（NOD）小鼠模型中，早期生活中的微生物暴露决定性激素水平并改变自身免疫的进展。肠道微生物的定植提高了血清睾酮水平，并保护NOD男性免受T1D的影响。将肠道微生物群从成年男性转移到未成熟女性改变了受体的微生物群，导致睾酮和代谢组学变化升高，胰岛炎症和自身抗体产生减少，以及强大的T1D保护。这些作用依赖于雄激素受体活性。因此，肠道微生物群落改变性激素水平，并调节高遗传风险个体的自身免疫性疾病命运。
Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.