Committee on Microbiology, The University of Chicago, Chicago, IL 60637, USA.
Immunity. 2013 Aug 22;39(2):400-12. doi: 10.1016/j.immuni.2013.08.013.
Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific pathogen-free nonobese diabetic (NOD) mice, females have 1.3-4.4 times higher incidence of type 1 diabetes (T1D). Germ-free (GF) mice lost the gender bias (female-to-male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some, but not all, lineages overrepresented in male mice supported a gender bias in T1D. Although protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive-feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene-expression analysis suggested pathways involved in protection of males from T1D by microbiota. Our results favor a two-signal model of gender bias, in which hormones and microbes together trigger protective pathways.
性别偏见和性激素在自身免疫性疾病中的作用已得到充分证实。在特定病原体无肥胖型糖尿病（NOD）小鼠中，女性患 1 型糖尿病（T1D）的发病率是男性的 1.3-4.4 倍。无菌（GF）小鼠失去了性别偏见（雌雄比例为 1.1-1.2）。雄性和雌性小鼠的肠道微生物群存在差异，这种趋势在雄性去势后发生逆转，证实了雄激素会影响肠道微生物群。用特定的微生物群定植 GF NOD 小鼠表明，雄性小鼠中过度表达的某些但不是所有谱系支持 T1D 的性别偏见。尽管男性的保护与血液雄激素浓度无关，但激素支持的选定微生物谱系的扩张可能作为一个正反馈机制，有助于自身免疫性疾病的性别二态性。基因表达分析表明，微生物群参与了男性对 T1D 的保护途径。我们的研究结果支持性别偏见的双信号模型，其中激素和微生物共同触发保护性途径。
