Dietary Arginine Supplementation of Mice Alters the Microbial Population and Activates Intestinal Innate Immunity

Abstract

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.

The crucial role of l-arginine in macrophage activation: What you need to know about it

“…It was discovered that L-arginine exerts pleiotropic and often contrasting effects on different immune cell populations (Chen et al, 2012;Feldmeyer et al, 2012;Kapp et al, 2014;Lamas et al, 2012;Maarsingh et al, 2008;Munder et al, 2013;Peranzoni et al, 2008;Pekarova et al, 2011;Raber et al, 2012;Ren et al, 2014;Xu et al, 2015;Yu et al, 2014). Interestingly, it was found that granulocyte functions and cytotoxicity of tumor antigen-specific human T cells are unimpaired by L-arginine depletion (Kapp et al, 2014;Munder et al, 2013).…”

Jian carp ( Cyprinus carpio var. Jian) intestinal immune responses, antioxidant status and tight junction protein mRNA expression are modulated via Nrf2 and PKC in response to dietary arginine deficiency

“…Nevertheless, no study has addressed the effect of dietary arginine on the intestinal inflammatory response in fish. In the rat intestine, administration of arginine decreased the mRNA expression of IL-1b [12]. Moreover, a previous study on juvenile Jian carp showed that arginine could regulate target of rapamycin (TOR) mRNA expression in the intestine [13].…”

Effects of dietary l-glutamine supplementation on specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine

“…For determining the expression of virulence factors, the 16S rRNA was used as the reference gene (Ren et al 2013e). Real-time PCR was performed according to our previous study (Ren et al 2014a). …”