Microbiome:低聚果糖/菊粉可直接调节黏膜免疫

Microbiome

2017-10-10Article

8.496

影响因子

原标题:不易消化的低聚糖无须改变肠道菌群,可直接调节宿主的激酶组以调控宿主的炎症响应

① 利用蛋白激酶组芯片,评估在无微生物存在时宿主肠道细胞对益生元(低聚果糖/菊粉)的信号响应;② 在Caco-2Bbe1肠道细胞系和内毒素诱导小鼠模型中,对鉴定出的信号通路进行功能验证;③ 暴露于益生元的肠上皮细胞对病原体诱导的丝裂原活化蛋白激酶(MAPK)和核转录因子κB(NF-κB)激活只有低反应性,且不具有含多个先天免疫信号通路的激酶组特征;④ 在灌喂益生元的小鼠中,因脂多糖(LPS)引起的炎症响应较弱,且不依赖于肠道菌群改变。

低聚果糖 菊粉 益生元 激酶组 脂多糖

图片

Title:
Non-digestible oligosaccharides directly regulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota

DOI:
10.1186/s40168-017-0357-4

Abstract & Authors展开

Abstract:
Background Prebiotics are non-digestible food ingredients that enhance the growth of certain microbes within the gut microbiota. Prebiotic consumption generates immune-modulatory effects that are traditionally thought to reflect microbial interactions within the gut. However, recent evidence suggests they may also impart direct microbe-independent effects on the host, though the mechanisms of which are currently unclear. Methods Kinome arrays were used to profile the host intestinal signaling responses to prebiotic exposures in the absence of microbes. Identified pathways were functionally validated in Caco-2Bbe1 intestinal cell line and in vivo model of murine endotoxemia. Results We found that prebiotics directly regulate host mucosal signaling to alter response to bacterial infection. Intestinal epithelial cells (IECs) exposed to prebiotics are hyporesponsive to pathogen-induced mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activations, and have a kinome profile distinct from non-treated cells pertaining to multiple innate immune signaling pathways. Consistent with this finding, mice orally gavaged with prebiotics showed dampened inflammatory response to lipopolysaccharide (LPS) without alterations in the gut microbiota. Conclusions These findings provide molecular mechanisms of direct host-prebiotic interactions to support prebiotics as potent modulators of host inflammation.

All Authors:
Richard Y Wu, Pekka Määttänen, Scott Napper, Erin Scruten, Bo Li, Yuhki Koike, Kathene C Johnson-Henry, Agostino Pierro, Laura Rossi, Steven R Botts, Michael G Surette, Philip M Sherman

First Authors:
Richard Y Wu

Correspondence:
Philip M Sherman

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