Hindgut-targeted delivery alpha-ketoglutarate pellets improves broiler intestinal redox and growth performance by activating uncoupling protein 2.

Glutamate metabolism is crucial for intestinal epithelial metabolism, but its availability is limited in the hindgut. We used a hindgut-targeted delivery system to deliver L-glutamate and its metabolite α-ketoglutarate (AKG) to investigate the effects of glutamate metabolites on broiler growth and to reveal the potential underlying mechanism. In a three-week feeding trial, fifty-four broilers were randomly divided into three treatments, basal diet (control), basal diet supplemented with 0.1 % L-glutamate (L-Glu) pellets and basal diet supplemented with 0.1 % AKG pellets. The growth performance, intestinal health, microbiota and ammonia nitrogen metabolism were examined. Then, RNA sequencing was adopted to reveal transcriptomic profile of cecal mucosal epithelial cells. Finally, the potential mechanism of AKG in regulating intestinal redox homeostasis was also investigated by in vitro cell model. The results demonstrated that hindgut-targeted delivery of AKG significantly increased average daily gain and decreased the feed-to-gain ratio (F/G), which is better than the effect of L-Glu. Although AKG did not significantly affect intestinal barrier function, inflammation, or microbiota composition, it markedly reduced serum levels of phenylalanine, tryptophan and valine, while significantly reduced ammonia content in cecal contents. Transcriptomic sequencing showed that AKG significantly downregulated oxidative phosphorylation (OXPHOS) in the cecal mucosa and reduced oxidative damage. In vitro experiments confirmed that AKG significantly reduced OXPHOS and alleviated oxidative damage in colonocytes. Further, cellular thermal shift assay (CETSA) and pharmacological study revealed that uncoupling protein 2 (UCP2) mediated the effect of AKG on redox status of colonocytes. Thus, hindgut-targeted delivery of AKG enhances broiler growth performance by activating UCP2 in intestinal epithelial cells, reducing OXPHOS and alleviating oxidative damage in the intestinal mucosa. These findings support precise strategies for regulating growth in poultry production.