Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
Diabetes. 2013 Apr;62(4):1238-44. doi: 10.2337/db12-0526. Epub 2012 Dec 28.
The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects. To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing. Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with β-cell autoimmunity. In addition, a dearth of the two most dominant Bifidobacterium species, Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with β-cell autoimmunity. We did not find increased fecal calprotectin or IgA as marker of inflammation in children with β-cell autoimmunity. Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.
肠道微生物群作为动物模型中自身免疫性糖尿病的调节剂的作用已得到充分证实,但关于 1 型人类糖尿病的数据尚不确定,并且基于仅包括少数研究对象的研究。为了排除糖尿病和 HLA 风险基因型对肠道微生物群的继发性影响,我们使用焦磷酸测序比较了至少有两种与糖尿病相关自身抗体的儿童(n = 18)与年龄、性别、早期喂养史和 HLA 风险基因型相匹配的自身抗体阴性儿童的肠道微生物群组成。主成分分析表明,产乳酸和丁酸盐的物种丰度低与β细胞自身免疫有关。此外,在具有β细胞自身免疫的儿童中,观察到两种最主要双歧杆菌属物种(青春双歧杆菌和假链双歧杆菌)的缺乏和拟杆菌属的丰度增加。我们没有发现β细胞自身免疫儿童的粪便钙卫蛋白或 IgA 增加作为炎症标志物。由于双歧杆菌和产丁酸盐的物种丰度低可能会对肠道上皮屏障功能和炎症产生不利影响,而拟杆菌属在 1 型糖尿病发展中的明显重要性尚不清楚,因此需要进行与肠道微生物组观察到的改变相关的功能研究。