A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice
A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice
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DOI：
10.2337/db13-1612
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发表时间：
2014-08-01
期刊：
影响因子：
7.7
通讯作者：
Hansen, Axel K.
中科院分区：
文献类型：
--
作者：
Hansen, Camilla Hartmann Friis;Krych, Lukasz;Hansen, Axel K.
早期生活中肠道环境的干预以前已被证明会影响糖尿病的发病率。因此，我们假设，无麸质（GF）饮食，已知降低1型糖尿病的发病率，将防止糖尿病的发展时，只在怀孕和哺乳期喂养。妊娠非肥胖糖尿病（NOD）小鼠喂食GF或标准饮食，直到所有幼崽断奶至标准饮食。生命早期的GF环境显著降低了糖尿病和胰岛炎的发病率。通过16S rRNA基因测序进行的肠道微生物群分析显示，不同饮食的母亲及其后代之间存在显著差异，其特征在于GF饮食组中Akkermansia，Proteobacteria和TM7数量增加。此外，在GF喂养的后代中，胰腺叉头盒P3调节性T细胞增加，肠道中的M2巨噬细胞基因标记物和紧密连接相关基因也增加，而促炎细胞因子的肠道基因表达减少。胰腺中表达粘膜整联蛋白α 4 β 7的T细胞比例增加表明该机制涉及肠道引发的免疫细胞向胰腺的运输增加。总之，在胎儿和出生后早期的GF饮食可以降低糖尿病的发病率。该机制可能涉及肠道微生物群的变化，并在肠道和胰腺中转移到较少的促炎免疫环境。
Early-life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known to decrease the incidence of type 1 diabetes, would protect against the development of diabetes when fed only during the pregnancy and lactation period. Pregnant nonobese diabetic (NOD) mice were fed a GF or standard diet until all pups were weaned to a standard diet. The early-life GF environment dramatically decreased the incidence of diabetes and insulitis. Gut microbiota analysis by 16S rRNA gene sequencing revealed a pronounced difference between both mothers and their offspring on different diets, characterized by increased numbers of Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells were increased in GF-fed offspring, as were M2 macrophage gene markers and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. An increased proportion of T cells in the pancreas expressing the mucosal integrin alpha 4 beta 7 suggests that the mechanism involves increased trafficking of gut-primed immune cells to the pancreas. In conclusion, a GF diet during fetal and early postnatal life reduces the incidence of diabetes. The mechanism may involve changes in gut microbiota and shifts to a less proinflammatory immunological milieu in the gut and pancreas.