Butyrate improves dextran sulfate sodium-induced enterotoxicity in broilers

Intestinal inflammation has emerged as a significant global concern in poultry farming, particularly due to its strong association with macrophage imbalance. Research has identified macrophages as critical target cells for butyrate, which collaboratively maintains intestinal immune homeostasis. This study delves into the regulatory effects of butyrate on macrophages to ameliorate enteritis in broiler chickens.

Our findings indicate that broilers treated with dextran sulfate sodium (DSS) exhibit reduced body weight and compromised intestinal mucosal integrity, characterized by increased intestinal permeability, elevated histological scores, diminished goblet cell numbers, reduced secretion of MUC2 protein, and decreased expression of tight junction proteins, alongside heightened oxidative stress and apoptotic responses. Notably, DSS treatment induces the polarization of M0 macrophages towards the pro-inflammatory M1 phenotype, thereby exacerbating intestinal inflammation. Conversely, butyrate supplementation facilitates the polarization of macrophages towards the anti-inflammatory M2 phenotype by inhibiting M1 polarization, thereby mitigating intestinal inflammation and promoting the restoration of the intestinal mucosal barrier. Further in vitro experiments demonstrated that butyrate regulates macrophage polarization through activation of the HDAC3/AMPK/PPARγ/Hippo/GLUT1 signaling pathway, ultimately exerting a beneficial effect.

Butyrate has been shown to facilitate M2 macrophage polarization by modulating cellular metabolic pathways, thereby ameliorating intestinal inflammation. This study underscores the clinical significance of immunometabolism in intestinal diseases and identifies potential therapeutic targets, serving as a valuable reference for the clinical management of enteritis in broilers.