Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.
Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.
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孕妇盲肠微生物群转移营救了早期寿命抗生素诱导的小鼠1型糖尿病的增强。
DOI：
10.1016/j.chom.2021.06.014
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发表时间：
2021-08-11
影响因子：
30.3
通讯作者：
Blaser MJ
中科院分区：
文献类型：
--
作者：
Zhang XS;Yin YS;Wang J;Battaglia T;Krautkramer K;Li WV;Li J;Brown M;Zhang M;Badri MH;Armstrong AJS;Strauch CM;Wang Z;Nemet I;Altomare N;Devlin JC;He L;Morton JT;Chalk JA;Needles K;Liao V;Mount J;Li H;Ruggles KV;Bonneau RA;Dominguez-Bello MG;Bäckhed F;Hazen SL;Blaser MJ
在NOD小鼠模型中，早期抗生素暴露扰乱肠道微生物群并加速1型糖尿病（T1D）的发展。在这里，我们发现，母体盲肠微生物群转移（CMT）的NOD小鼠后，早期生活抗生素扰动在很大程度上挽救了诱导的T1D增强。肠道微生物组的恢复是显著和持久的，补救了浮游生物耗尽的多样性、特定分类群的相对丰度和代谢途径。CMT还保护免受干扰的代谢物和正常化的先天性和适应性免疫效应。CMT恢复了回肠microRNA和组蛋白基因表达调控的主要模式。进一步的实验表明，在涉及CD 44、TLR 2和Reg 3 γ的先天肠道免疫网络中，肠道微生物群调节的T1 D保护机制以Reg 3 γ为中心。这种调节影响下游免疫张力，这可能导致对组织特异性T1D损伤的保护。使用早期抗生素增强T1D的小鼠模型，Zhang等人表明随后的母体盲肠微生物群转移减少了疾病。对肠道微生物组和代谢、回肠壁基因表达和调节以及先天性和适应性免疫效应物的恢复作用表明肠道微生物群调节的T1D保护机制。
Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury. Using a mouse model where early-life antibiotics enhances T1D, Zhang et al. show that subsequent maternal cecal microbiota transfer reduces illness. The restorative effects on intestinal microbiome and metabolism, ileal wall gene expression and regulation, and innate and adaptive immune effectors suggest a gut microbiota-regulated T1D protective mechanism.
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影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
48
作者：
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通讯作者：
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7.8
作者：
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通讯作者：
Ong, Chin-Tong
影响因子：
4.4
作者：
Forestier, Claire;Takaki, Toshiyuki;Porcelli, Steven A.
通讯作者：
Porcelli, Steven A.
影响因子：
5.9
作者：
FAITH, DP
通讯作者：
FAITH, DP