Chestnut Tannin Improves Growth Performance and Intestinal Health of Broilers Challenged with Necrotic Enteritis via the cGAS-STING-Ferroptosis Pathway

This study aimed to investigate the impacts of chestnut tannin (CT) on growth performance, immune response, and intestinal health of broilers challenged with necrotic enteritis (NE) through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-ferroptosis pathway. A total of 240 one-day-old male Cobb 500 broilers (44.54 ± 0.51 g) were randomly divided into four groups, including a Control group, NE group, 500 mg/kg CT group (L-CT), and 1000 mg/kg CT group (H-CT), with six replicates per group and ten broilers per replicate. Sporulated coccidia oocysts on day 14 and <i>Clostridium perfringens</i> solution from days 19 to 21 were given to all broilers except the Control group through oral administration to establish the NE infection model. The results demonstrated that dietary supplementation with CT improved (<i>p</i> < 0.05) growth performance, intestinal morphology, and intestinal mucosal barrier function of broilers challenged with NE. CT supplementation decreased (<i>p</i> < 0.05) interleukin (IL)-1β, IL-6, type I interferon, interferon-γ, and tumor necrosis factor-α concentrations and increased (<i>p</i> < 0.05) IL-10 concentration in the jejunal mucosa. Furthermore, CT supplementation decreased (<i>p</i> < 0.05) Fe²⁺ concentration, malondialdehyde concentration, mitochondrial DNA level, and mitochondrial reactive oxygen species level in the jejunal mucosa. Broilers under NE challenge had upregulated (<i>p</i> < 0.05) jejunal protein expression of cGAS, STING, phospho-TANK-binding kinase 1, phospho-interferon regulatory factor 7, phospho-nuclear factor kappa B, ferroptosis suppressor protein 1, prostaglandin-endoperoxide synthase 2, acyl-CoA synthetase long-chain family member 4, WD repeat domain phosphoinositide-interacting protein 2, nuclear receptor co activator factor 4 and autophagy related protein 5 and downregulated (<i>p</i> < 0.05) glutathione peroxidase 4, ferritin heavy chain 1, ferritin light chain and ferroportin 1 compared with the Control group, while the supplementation of CT reversed these effects. In conclusion, CT improved intestinal inflammatory damage of broilers challenged with NE by inhibiting the cGAS-STING-ferroptosis pathway, which was more effective at a dose of 1000 mg/kg in this study.