Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility.
Modulation of the diet and gastrointestinal microbiota normalizes systemic inflammation and β-cell chemokine expression associated with autoimmune diabetes susceptibility.
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DOI：
10.1371/journal.pone.0190351
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hessner MJ
中科院分区：
文献类型：
--
作者：
Henschel AM;Cabrera SM;Kaldunski ML;Jia S;Geoffrey R;Roethle MF;Lam V;Chen YG;Wang X;Salzman NH;Hessner MJ
与现代生活方式相关的环境变化可能是1型糖尿病（T1 D）发病率上升的原因。我们之前对T1 D家族和BioBreeding（BB）大鼠模型的研究已经确定了与糖尿病易感性相关的外周炎症状态，与模式识别受体连接一致，但与疾病进展无关。在此，与对照菌株相比，自发性糖尿病BB DRlyp/lyp和糖尿病诱导型BB DR+/+断奶仔猪的胰岛提供了标准谷物饮食，其表达与包括许多细胞因子/趋化因子的微生物抗原暴露一致的稳健的促炎转录程序。通过将DR+/+断奶仔猪转变为无麸质水解酪蛋白饲料（HCD）或用抗生素治疗以改变/减少模式识别受体配体暴露，研究了该表型对饲料和胃肠道微生物群的依赖性。细菌16 S rRNA基因测序显示，这些处理改变了回肠和盲肠微生物群，增加了厚壁菌门：拟杆菌门的比例以及乳酸杆菌和丁酸盐生产分类群的相对丰度。虽然这些条件没有使DR+/+大鼠白细胞对离体TLR刺激的固有高反应性正常化，但它们使血浆细胞因子水平、血浆TLR 4活性水平、促炎性胰岛转录组和β细胞趋化因子表达正常化。在淋巴细胞减少的DRlyp/lyp大鼠中，HCD降低了T1 D的发病率，并且在这种饮食中引入谷蛋白诱导了胰岛趋化因子的表达并消除了对糖尿病的保护。总的来说，这些研究将BB大鼠胰岛水平免疫细胞募集潜力（如通过β细胞趋化因子表达测量的）与遗传控制的免疫高反应性和先天性炎症状态联系起来，这些免疫高反应性和先天性炎症状态可以通过饮食和肠道微生物群调节。
Environmental changes associated with modern lifestyles may underlie the rising incidence of Type 1 diabetes (T1D). Our previous studies of T1D families and the BioBreeding (BB) rat model have identified a peripheral inflammatory state that is associated with diabetes susceptibility, consistent with pattern recognition receptor ligation, but is independent of disease progression. Here, compared to control strains, islets of spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ weanlings provided a standard cereal diet expressed a robust proinflammatory transcriptional program consistent with microbial antigen exposure that included numerous cytokines/chemokines. The dependence of this phenotype on diet and gastrointestinal microbiota was investigated by transitioning DR+/+ weanlings to a gluten-free hydrolyzed casein diet (HCD) or treating them with antibiotics to alter/reduce pattern recognition receptor ligand exposure. Bacterial 16S rRNA gene sequencing revealed that these treatments altered the ileal and cecal microbiota, increasing the Firmicutes:Bacteriodetes ratio and the relative abundances of lactobacilli and butyrate producing taxa. While these conditions did not normalize the inherent hyper-responsiveness of DR+/+ rat leukocytes to ex vivo TLR stimulation, they normalized plasma cytokine levels, plasma TLR4 activity levels, the proinflammatory islet transcriptome, and β-cell chemokine expression. In lymphopenic DRlyp/lyp rats, HCD reduced T1D incidence, and the introduction of gluten to this diet induced islet chemokine expression and abrogated protection from diabetes. Overall, these studies link BB rat islet-level immunocyte recruiting potential, as measured by β-cell chemokine expression, to a genetically controlled immune hyper-responsiveness and innate inflammatory state that can be modulated by diet and the intestinal microbiota.
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DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
5
作者：
Chen, Y-G;Mordes, J. P.;Blankenhorn, E. P.;Kashmiri, H.;Kaldunski, M. L.;Jia, S.;Geoffrey, R.;Wang, X.;Hessner, M. J.
通讯作者：
Hessner, M. J.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
6
作者：
Bernardes, Emerson Soares;Silva, Neide M.;Roque-Barreira, Maria Cristina
通讯作者：
Roque-Barreira, Maria Cristina
影响因子：
4.6
作者：
English, K.;Ryan, J. M.;Mahon, B. P.
通讯作者：
Mahon, B. P.