Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
Microbiome. 2017 Oct 10;5(1):135. doi: 10.1186/s40168-017-0357-4.
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.
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.
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.
These findings provide molecular mechanisms of direct host-prebiotic interactions to support prebiotics as potent modulators of host inflammation.
益生元是指无法被人体消化的食物成分，能够促进肠道微生物群中某些微生物的生长。益生元的摄入会产生免疫调节作用，这些作用传统上被认为反映了肠道内微生物的相互作用。然而，最近的证据表明，它们也可能对宿主产生直接的、与微生物无关的影响，尽管其机制目前尚不清楚。
采用激酶组芯片技术来分析宿主肠道在没有微生物存在的情况下对益生元暴露的信号反应。在 Caco-2Bbe1 肠细胞系和内毒素血症的小鼠体内模型中对鉴定出的途径进行了功能验证。
我们发现，益生元可以直接调节宿主黏膜信号，从而改变对细菌感染的反应。与未处理的细胞相比，暴露于益生元的肠上皮细胞（IECs）对病原体诱导的丝裂原活化蛋白激酶（MAPK）和核因子 kappa B（NF-κB）激活的反应性降低，并且其激酶组谱与多种固有免疫信号通路有关。与这一发现一致的是，经口给予益生元的小鼠对脂多糖（LPS）的炎症反应减弱，而肠道微生物群没有变化。
这些发现为宿主-益生元相互作用的直接分子机制提供了依据，支持将益生元作为宿主炎症的有效调节剂。
