Microbiome:1型糖尿病易感基因可影响肠道菌群
创作:aluba 审核:aluba 2018年03月14日
  • 在非肥胖糖尿病(NOD)小鼠模型中鉴定出NOD相关菌群;
  • 在Idd3及Idd5基因位点引入保护性等位基因(IL2、Ctla4、Slc11a1及Acadl)可显著改变NOD相关菌群;
  • 引入保护性等位基因的小鼠表现出肠道内免疫调节通路的恢复,相应通路的恢复也可由靶向IL-2的治疗完成;
  • 在TwinsUK的健康人队列中,选取IL-2通路上与1型糖尿病风险相关的等位基因;
  • 这些等位基因与拟杆菌属、毛螺菌科、疣微菌科相关,与NOD小鼠中保护性等位基因引起变化的菌群相似。
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aluba
在小鼠及人中,存在一些与IL-2通路相关的1型糖尿病的易感基因,而这些等位基因与肠道菌群的组成相关。
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Microbiome [IF:11.607]

Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota

1型糖尿病的易感等位基因与不同的肠道菌群变化相关

10.1186/s40168-018-0417-4

2018-02-17, Article

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BACKGROUND: Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort.
RESULTS: Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse.
CONCLUSIONS: These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.

First Authors:
Jane A Mullaney

Correspondence Authors:
Emma E Hamilton-Williams

All Authors:
Jane A Mullaney,Juliette E Stephens,Mary-Ellen Costello,Cai Fong,Brooke E Geeling,Patrick G Gavin,Casey M Wright,Timothy D Spector,Matthew A Brown,Emma E Hamilton-Williams

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