Dietary Arginine Supplementation of Mice Alters the Microbial Population and Activates Intestinal Innate Immunity
Dietary Arginine Supplementation of Mice Alters the Microbial Population and Activates Intestinal Innate Immunity
复制标题
小鼠膳食精氨酸补充剂改变微生物群并激活肠道先天免疫
DOI：
10.3945/jn.114.192120
复制
发表时间：
2014-06-01
影响因子：
4.2
通讯作者：
Wu, Guoyao
中科院分区：
文献类型：
--
作者：
Ren, Wenkai;Chen, Shuai;Wu, Guoyao
目前，对精氨酸在肠道免疫系统稳态中的功能知之甚少。本研究旨在验证膳食精氨酸补充剂可能改变小鼠肠道微生物群和先天免疫的假设。小鼠饲喂基础日粮（含0.93%L-精氨酸; g/g）或基础日粮中添加0.5%L-精氨酸14 d。我们研究了肠道微生物群的组成，先天免疫的激活，以及小鼠空肠，回肠或结肠中的Toll样受体（Tlrs），促炎细胞因子和抗菌剂的表达。通过蛋白质印迹法分析空回肠中的信号转导通路活化，包括TLR 4-活化B细胞的核因子κ-轻链增强子（NF-κ B）、促分裂原活化蛋白激酶（MAPK）和磷酸肌醇-3激酶（PI 3 K）/PI 3 K蛋白激酶B（Akt）。定量聚合酶链反应分析显示，与对照组相比，精氨酸补充诱导（P < 0.05）厚壁菌与拟杆菌的比例发生变化，有利于空肠（0.33 +/- 0.04 vs. 1.0 +/- 0.22）和回肠（0.20 +/- 0.08 vs. 1.0 +/- 0.27）中的拟杆菌。这一发现与空肠和回肠中先天免疫系统的更大（P < 0.05）激活（包括TLR信号传导）以及促炎细胞因子、分泌性免疫球蛋白A、粘蛋白和潘氏抗菌剂的表达一致。最后，补充精氨酸降低（P < 0.05）空回肠NF-κ B、MARK和PI 3 K-Akt信号通路蛋白的表达，但分别激活（P < 0.05）p38和c-Jun N-末端蛋白激酶。总之，小鼠的饮食精氨酸补充改变了肠道微生物群，有助于通过NF-κ B、MARK和PI 3 K-磷酸化Akt信号传导途径激活肠道先天免疫。
Currently, little is known about the function of arginine in the homeostasis of the intestinal immune system. This study was conducted to test the hypothesis that dietary arginine supplementation may alter intestinal microbiota and innate immunity in mice. Mice were fed a basal diet (containing 0.93% L-arginine; grams per gram) or the basal diet supplemented with 0.5% L-arginine for 14 d. We studied the composition of intestinal microbiota, the activation of innate immunity, and the expression of toll-like receptors (Tlrs), proinflammatory cytokines, and antimicrobials in the jejunum, ileum, or colon of mice. Signal transduction pathway activation in the jejunum and ileum, including TLR4-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), mitogen-activated protein kinase (MAPK), and phosphoinositide-3 kinase (PI3K)/PI3K protein kinase B (Akt), was analyzed by Western blotting. Quantitative polymerase chain reaction analysis revealed that arginine supplementation induced (P < 0.05) a shift in the Firmicutes-to-Bacteroidetes ratio to favor Bacteroidetes in the jejunum (0.33 +/- 0.04 vs. 1.0 +/- 0.22) and ileum (0.20 +/- 0.08 vs. 1.0 +/- 0.27) compared with the control group. This finding coincided with greater (P < 0.05) activation of the innate immune system, including TLR signaling, as well as expression of proinflammatory cytokines, secretory immunoglobulin A, mucins, and Paneth antimicrobials in the jejunum and ileum. Finally, arginine supplementation reduced (P < 0.05) expression of the proteins for NF-kappa B, MARK, and PI3K-Akt signaling pathways but activated (P < 0.05) p38 and c-Jun N-terminal protein kinase in the jejunum and the ileum, respectively. Collectively, dietary arginine supplementation of mice changes the intestinal microbiota, contributing to the activation of intestinal innate immunity through NF-kappa B, MARK, and PI3K-phosphorylated Akt signaling pathways.