Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China; and.
Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China; and
J Nutr. 2014 Jun;144(6):988-95. doi: 10.3945/jn.114.192120. Epub 2014 Mar 26.
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-κB), 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-κB, MAPK, 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-κB, MAPK, and PI3K-phosphorylated Akt signaling pathways.
目前，人们对精氨酸在肠道免疫系统稳态中的作用知之甚少。本研究旨在验证以下假设：饮食补充精氨酸可能会改变小鼠的肠道微生物群和固有免疫。将小鼠喂食基础饮食（含 0.93%l-精氨酸；克/克）或基础饮食补充 0.5%l-精氨酸 14 天。我们研究了肠道微生物群的组成、固有免疫的激活以及 TLR（Toll 样受体）、促炎细胞因子和抗菌肽在空肠、回肠或结肠中的表达。通过 Western blot 分析了空肠和回肠中 TLR4-核因子 kappaB（NF-κB）、丝裂原活化蛋白激酶（MAPK）和磷酸肌醇 3 激酶（PI3K）/PI3K-蛋白激酶 B（Akt）信号转导通路的激活。定量聚合酶链反应分析显示，精氨酸补充使厚壁菌门与拟杆菌门的比例向有利于拟杆菌门的方向转变，空肠（0.33±0.04 比 1.0±0.22）和回肠（0.20±0.08 比 1.0±0.27）的比例高于对照组。这一发现与固有免疫系统的更大激活（P<0.05）相一致，包括 TLR 信号，以及空肠和回肠中促炎细胞因子、分泌型免疫球蛋白 A、粘蛋白和潘氏抗菌肽的表达。最后，精氨酸补充降低了空肠和回肠中 NF-κB、MAPK 和 PI3K-Akt 信号通路蛋白的表达，但分别激活了 p38 和 c-Jun N 末端蛋白激酶。总之，饮食补充精氨酸改变了小鼠的肠道微生物群，通过 NF-κB、MAPK 和 PI3K-磷酸化 Akt 信号通路促进肠道固有免疫的激活。
