Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome.

Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome.
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DOI:
10.1371/journal.pone.0078687
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Rajagopalan G
Rajagopalan G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Marietta EV;Gomez AM;Yeoman C;Tilahun AY;Clark CR;Luckey DH;Murray JA;White BA;Kudva YC;Rajagopalan G

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人类和动物研究强烈表明,膳食麸质可能在1型糖尿病(T1D)的发病机制中发挥因果作用。然而,其机制尚未阐明。最近的报道表明,肠道微生物组对T1D的发病率有重要影响。由于已知饮食可以塑造肠道微生物组的组成,我们使用非肥胖糖尿病(NOD)小鼠研究了肠道微生物组的变化是否可以分别归因于含麸质和无麸质饮食的促糖尿病和抗糖尿病作用。NOD小鼠分别饲喂含谷蛋白食物(GCC)和无谷蛋白食物(GFC)。糖尿病的发病率是通过每两周使用血糖仪监测血糖水平来确定的。通过对来自粪便样本的16S rRNA扩增子进行测序,分析肠道微生物组组成。首先,GFC喂养的NOD小鼠高血糖发生率与预期的一样高,而GFC喂养的NOD小鼠高血糖发生率明显降低。其次,在比较粪便微生物组时,GCC小鼠肠道微生物组中双歧杆菌(Bifidobacterium)、Tannerella和Barnesiella种类增加(p分别为0.03、0.02和0.02),而饲喂GFC的NOD小鼠肠道微生物组中Akkermansia种类增加(p = 0.02)。第三,两种被评估的无麸质食物,无论是蛋清(EW-GFC)还是酪蛋白(C-GFC),都显著降低了高血糖的发生率。有趣的是,EW-GFC小鼠的肠道微生物组与C-GFC小鼠相似。最后,在无谷蛋白饮食中添加谷蛋白逆转了其抗糖尿病作用,减少了阿克曼氏菌种类,增加了双歧杆菌、Tannerella和Barnesiella,这表明谷蛋白的存在直接导致了饮食的促糖尿病作用,它决定了肠道菌群。因此,我们的新研究表明,膳食麸质可以通过改变肠道微生物群来调节T1D的发病率。
Human and animal studies strongly suggest that dietary gluten could play a causal role in the etiopathogenesis of type 1 diabetes (T1D). However, the mechanisms have not been elucidated. Recent reports indicate that the intestinal microbiome has a major influence on the incidence of T1D. Since diet is known to shape the composition of the intestinal microbiome, we investigated using non-obese diabetic (NOD) mice whether changes in the intestinal microbiome could be attributed to the pro- and anti-diabetogenic effects of gluten-containing and gluten-free diets, respectively. NOD mice were raised on gluten-containing chows (GCC) or gluten-free chows (GFC). The incidence of diabetes was determined by monitoring blood glucose levels biweekly using a glucometer. Intestinal microbiome composition was analyzed by sequencing 16S rRNA amplicons derived from fecal samples. First of all, GCC-fed NOD mice had the expected high incidence of hyperglycemia whereas NOD mice fed with a GFC had significantly reduced incidence of hyperglycemia. Secondly, when the fecal microbiomes were compared, Bifidobacterium, Tannerella, and Barnesiella species were increased (p = 0.03, 0.02, and 0.02, respectively) in the microbiome of GCC mice, where as Akkermansia species was increased (p = 0.02) in the intestinal microbiomes of NOD mice fed GFC. Thirdly, both of the gluten-free chows that were evaluated, either egg white based (EW-GFC) or casein based (C-GFC), significantly reduced the incidence of hyperglycemia. Interestingly, the gut microbiome from EW-GFC mice was similar to C-GFC mice. Finally, adding back gluten to the gluten-free diet reversed its anti-diabetogenic effect, reduced Akkermansia species and increased Bifidobacterium, Tannerella, and Barnesiella suggesting that the presence of gluten is directly responsible for the pro-diabetogenic effects of diets and it determines the gut microflora. Our novel study thus suggests that dietary gluten could modulate the incidence of T1D by changing the gut microbiome.
DOI: 10.1371/journal.pone.0036095
发表时间: 2012
期刊: PloS one
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发表时间: 2003-10-01
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发表时间: 2010-07
影响因子: 5.1
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DOI: 10.1542/peds.109.5.833
发表时间: 2002-05-01
期刊: PEDIATRICS
影响因子: 8
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