Department of Immunology; University of Toronto; Toronto, ON Canada; Program in Genetics and Genomic Biology; The Hospital for Sick Children; Toronto, ON Canada.
Division of Infectious Diseases; University of Colorado; Aurora, CO USA.
Gut Microbes. 2014 Jul 1;5(4):485-93. doi: 10.4161/gmic.29795. Epub 2014 Jul 9.
Despite growing evidence for a causal role of environmental factors in autoimmune diseases including the rise in disease frequencies over the past several decades we lack an understanding of how particular environmental exposures modify disease risk. In addition, many autoimmune diseases display sex-biased incidence, with females being disproportionately affected but the mechanisms underlying this sex bias remain elusive. Emerging evidence suggests that both host metabolism and immune function is crucially regulated by the intestinal microbiome. Recently, we showed that in the non-obese diabetic (NOD) mouse model of Type 1 Diabetes (T1D), the gut commensal microbial community strongly impacts the pronounced sex bias in T1D risk by controlling serum testosterone and metabolic phenotypes (1). Here we present new data in the NOD model that explores the correlations between microbial phylogeny, testosterone levels, and metabolic phenotypes, and discuss the future of microbiome-centered analysis and microbe-based therapeutic approaches in autoimmune diseases.
尽管越来越多的证据表明环境因素在自身免疫性疾病中起着因果作用，包括过去几十年疾病频率的上升，但我们仍不了解特定的环境暴露如何改变疾病风险。此外，许多自身免疫性疾病表现出性别偏向的发病率，女性受到不成比例的影响，但这种性别偏差的机制仍然难以捉摸。新出现的证据表明，宿主代谢和免疫功能都受到肠道微生物组的严格调控。最近，我们发现，在非肥胖型糖尿病（NOD）小鼠 1 型糖尿病（T1D）模型中，肠道共生微生物群落通过控制血清睾酮和代谢表型强烈影响 T1D 风险的显著性别偏向（1）。在这里，我们在 NOD 模型中提出了新的数据，探讨了微生物系统发育、睾酮水平和代谢表型之间的相关性，并讨论了以微生物组为中心的分析和基于微生物的治疗方法在自身免疫性疾病中的未来。
