Impact of sodium butyrate on lipopolysaccharide-induced inflammatory response in zebrafish.

Butyrate is a short-chain fatty acid produced by intestinal bacteria during the fermentation of dietary fibers and has shown potential in modulating inflammatory responses. Herein, we investigated how sodium butyrate exerts dual, dose-dependent regulation of innate immunity using the zebrafish model of lipopolysaccharide (LPS)-induced inflammation. Our results demonstrated that at low concentrations (3 mM), sodium butyrate suppressed LPS-driven pro-inflammatory mediators (il1β, cebpβ, irg1l) while restoring anti-inflammatory and tissue-repair genes (lyz, il8, elf3). Conversely, high doses (30 mM) amplified inflammatory pathways, highlighting a critical therapeutic balance. Sodium butyrate further attenuated immune cell recruitment, reducing macrophage and neutrophil migration to injury sites by 40-60 % at 3 mM and more robustly at 20 mM. In addition, sodium butyrate modulated chemokine dynamics, e.g., ccl20a.3 suppression, and enhanced genes critical for tissue repair, e.g., anxa2a, s100a10b, and NF-κB signaling. These findings indicate sodium butyrate's dual role as both an anti-inflammatory agent and a potential pro-inflammatory trigger, contingent on concentration. These findings provide seminal information on the sodium butyrate-modulated innate immune response, which will help further explore the molecular role of this chemical. The study also highlights the necessity of precise dosing to harness its therapeutic benefits while avoiding adverse immune activation, offering critical insights for treating inflammatory diseases.