Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.
Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.
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DOI：
10.1111/j.1574-695x.2012.00978.x
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发表时间：
2012-08
影响因子：
--
通讯作者：
Shi HN
中科院分区：
文献类型：
--
作者：
Foye OT;Huang IF;Chiou CC;Walker WA;Shi HN
肠道相关免疫的不成熟可能导致与肠道感染相关的儿科死亡率。采用小鼠模型模拟婴儿肠道疾病，以确定益生菌、嗜酸乳杆菌（La）、益生元、菊粉或两者（synbiotic, syn）对病原体诱导的炎症反应、NF-κB和Smad 7信号的影响。新生小鼠每两周接种一次La、菊粉或syn，连续4周，并在5周时用啮齿柠檬酸杆菌（Cr）攻毒。小鼠肠上皮细胞（CMT93）暴露于Cr以测定NF-Kappa B和Smad 7水平的时间变化。与对照组相比，经La、菊粉和syn预处理的小鼠在Cr感染后肠道炎症减轻，这与La、菊粉和syn动物体内细菌定植显著减少有关。我们的研究结果进一步表明，在syn处理的小鼠中，宿主对Cr感染的防御与结肠IL-10和转化生长因子-β表达的增强以及NF-κB的抑制有关，而syn、La或菊粉预处理的小鼠则减弱了Cr诱导的Smad 7表达。cr感染和肿瘤坏死因子刺激后，CMT93细胞内存在Smad - 7和NF-κB积聚。因此，这些结果表明，益生菌、La、益生元胰岛素或合成菌可能通过影响NF-κB和Smad 7信号传导的机制，促进宿主保护性免疫，减轻cr诱导的肠道炎症。
Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-β expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling.