Early Gut Microbiota Intervention Suppresses DSS-Induced Inflammatory Responses by Deactivating TLR/NLR Signalling in Pigs.

Early Gut Microbiota Intervention Suppresses DSS-Induced Inflammatory Responses by Deactivating TLR/NLR Signalling in Pigs.
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早期肠道菌群干预通过停用猪的 TLR/NLR 信号传导来抑制 DSS 诱导的炎症反应

DOI:
10.1038/s41598-017-03161-6
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发表时间:
2017-06-12
期刊:
影响因子:
4.6
通讯作者:
Chen D
Chen D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xiao Y;Yan H;Diao H;Yu B;He J;Yu J;Zheng P;Mao X;Luo Y;Chen D

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最近的宏基因组学研究表明,先天性和适应性免疫表型可以通过激活宿主细胞上的模式识别受体(PRR)介导的肠道微生物-宿主相互作用来编程。在这项研究中,我们使用了两个非常不同的猪系(约克郡和西藏)来测试肠道微生物群移植可以将某些免疫学特征从供体转移到受体的假设。将这两个猪系的粪便微生物群移植到健康的商品杂交新生仔猪中,以建立“西藏干预”和“约克夏干预”猪模型。然后,使用葡聚糖硫酸钠(DSS)诱导急性结肠炎,其激活“Yorkshire干预”仔猪的结肠组织中的Toll-/NOD样受体(TLR/NLR)信号传导,导致促炎细胞因子和免疫细胞增加并引起肠道损伤。相反,DSS给药对“西藏干预”仔猪的影响很小,在DSS给药后,未显示出显著的炎症,细胞因子、免疫细胞或信号分子(包括TLR、NLR、MYD 88和NF-κB)未发生变化。这些结果表明,接种西藏微生物群的猪获得了对实验性结肠炎的相对较强的抗性,表明宿主的基因型有助于其肠道微生物群落的独特性,而微生物群在编程宿主的免疫表型中起着至关重要的作用。
Recent metagenomic studies suggest that innate and adaptive immune phenotypes can be programmed via gut microbiota-host interactions mediated via activation of pattern recognition receptors (PRRs) on host cells. In this study, we used two extremely different pig lines (the Yorkshire and the Tibetan) to test the hypothesis that the transplantation of gut microbiota could transfer certain immunologic characteristics from donor to recipient. The faecal microbiota of these two pig lines was transplanted in healthy commercial hybrid newborn piglets to establish the “Tibetan-intervened” and “Yorkshire-intervened” porcine models. Then, acute colitis was induced using dextran sulphate sodium (DSS), which activated Toll-/NOD-like receptor (TLR/NLR) signalling in the colonic tissues of the “Yorkshire-intervened” piglets, leading to increases in pro-inflammatory cytokines and immune cells and causing intestinal injuries. Conversely, DSS administration had little influence on the “Tibetan-intervened” piglets, which showed no significant inflammation and no changes in cytokines, immune cells, or signalling molecules, including TLRs, NLRs, MYD88 and NF-κB, after DSS treatment. These results indicate that pigs inoculated with the Tibetan microbiota acquired relatively strong resistance to experimental colitis, suggesting that the genotype of the host contributes to the uniqueness of its intestinal microbial community, whereas the microbiota plays a vital role in programming the immune phenotypes of the host.