肠道微生物组的性别差异驱动了对自身免疫的荷尔蒙依赖调节
Janet G M Markle1, Daniel N Frank, Steven Mortin-Toth
1Program in Genetics and Genome Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
概括
早期的肠道微生物影响性激素,并保护小鼠免受1型糖尿病 (T1D) 的影响. 微生物转移可以通过改变激素水平和减少自身免疫反应来给予保护.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 内分泌学 在内分泌学.
背景情况:
- 1型糖尿病 (T1D) 等自身免疫性疾病不成比例地影响女性.
- 性激素和微生物暴露是已知的自身免疫性疾病的调节者.
- 微生物群,性激素和自身免疫之间的相互作用需要进一步研究.
研究的目的:
- 调查早期微生物暴露在调节性激素水平中的作用.
- 确定微生物殖民是否可以在高风险模型中预防自身免疫性疾病的进展.
- 阐明微生物群通过性激素影响自身免疫的机制.
主要方法:
- 使用非肥胖糖尿病 (NOD) 鼠标模型进行1型糖尿病研究.
- 向生命早期的NOD小鼠注射开始性微生物.
- 从成年男性进行便微生物移植到不成熟的女性.
- 测量了血清激素水平,自身抗体和小岛炎症.
- 评估了雄激素受体活性的作用.
主要成果:
- 在雄性NOD小鼠中,共体微生物殖民导致血清丸激素水平升高,从而提供了对T1D的保护.
- 微生物群从雄性转移到雌性改变了受体激素配置,减少了自身免疫标记物,并预防了T1D.
- 这些保护作用依赖于雄激素受体信号传递.
结论:
- 早期的微生物暴露是性激素水平和自身免疫性疾病结果的关键决定因素.
- 肠道微生物群可以被操纵来改变性激素配置,并给予对自身免疫的保护.
- 准肠道微生物群代表了对自身免疫性疾病的潜在治疗策略,特别是在遗传敏感的个体中.
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