Nitric Oxide Synthase Regulates Gut Microbiota Homeostasis by ERK-NF-κB Pathway in Shrimp

Abstract

The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimp Marsupenaeus japonicus. The expression of Nos and the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected with Vibrio anguillarum. After RNA interference of Nos or treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically, V. anguillarum infection increased NO level via upregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogens via the ERK-dorsal pathway in shrimp.

Effects of Inducible Nitric Oxide Synthase (iNOS) Gene Knockout on the Diversity, Composition, and Function of Gut Microbiota in Adult Zebrafish

“…This alteration could increase infection risks, emphasizing NO’s crucial role in gut pathogen control. Conversely, a decrease in Vibrio, which is normally controlled by NO-mediated immune pathways, indicates a disruption in microbial regulation [ 42 ].…”

Advances in post-translational modifications of proteins and cancer immunotherapy

“…The progression and inhibition of breast cancer are significantly related to the phosphorylation of upstream and downstream regulatory factors of nitric oxide (NO) ( 21 ). The growth and proliferation of breast cancer cells are partly induced by NO synthase, which maintains the phosphorylation of Akt and mitogen-activated protein kinase 1/2 (extracellular signal-regulated protein kinases 1 and 2 [ERK1/2]) ( 22 , 23 ). However, a high NO concentration can induce apoptosis of breast cancer cells through dephosphorylation of Akt and ERK ( 24 ).…”

The Reactive Species Interactome - Mitochondria Axis

“…Interestingly, brain damage due to extensive stroke lead to gut bacterial dysbiosis, which also affects immune system, thus contributing to pro-inflammation, and systemic oxidative distress [128,152]. In addition, regarding notable NOS enzyme, the gut ba cterial microbiota is regulated by NO produced by NOS, while bacterial infection can lead to both upregulation of NOS and increase in NO content, which in turn stimule the immune response [153]. Furthermore, in mice, lactic acid bacteria, including Lactobacillus rhamnosus and Lactobacillus reuteri, contribute to reduce uric acid in serum and urine, through reduction in XOR activity, by increasing SCFAs generation [154].…”