Dietary alpha-ketoglutarate enhances intestinal immunity by Th17/Treg immune response in piglets after lipopolysaccharide challenge

Alpha-ketoglutarate (AKG) is important for improving intestinal and systemic immune function. This study aimed to explore whether AKG enhances gut immunity in lipopolysaccharide (LPS)-challenged piglets by modulating the immune-related helper T cells 17 (Th17)/regulatory T cells (Treg) balance pathway. A 2 x 2 factor design was used on 24 pigs, with the major factors being diet (basal diet or 1% AKG diet) and immunological challenge (saline or LPS). Piglets were fed with a basal or AKG diet for 21 d and then received intraperitoneal injection of LPS or saline. The results demonstrated that AKG supplementation enhanced growth performance compared with the control group (P < 0.05). AKG improved the ileal morphological structure (P < 0.01). Finally, AKG supplementation increased interleukin (IL)-10, transforming growth factor beta-1, forkhead box P3, and signal transducer and activator of transcription 5 genes expression whereas decreasing IL-6, IL-8, IL-1 & beta;, tumor necrosis factor-& alpha;, IL-17, IL-21, signal transducer and activator of transcription 3 and rar-related orphan receptor c genes expression (P < 0.05). These findings suggested that dietary AKG can improve the growth performance of piglets. Meanwhile, dietary AKG can alleviate LPS-induced intestinal inflammation through Th17/Treg immune response signaling pathway. Lay Summary Immature digestive and immune systems cause a variety of problems. The balance of helper Tcells 17 (Th17) and regulatory T cells (Treg) is critical in maintaining normal immune function in animals. Piglets' growth performance and immune function are all influenced by alpha-ketoglutarate (AKG). However, how AKG exerts its effect on intestinal immunity in piglets through modulating the immune signaling of Th17/Treg biology has not been explored. In this study, an inflammation model was established by lipopolysaccharide (LPS) injection. This study was to test the hypothesis that AKG can enhance growth performance and attenuate LPS-challenged intestinal inflammation by modulating Th17/Treg response. We concluded that dietary AKG can improve the growth performance of piglets. Dietary AKG alleviated intestinal inflammation induced by LPS through the Th17/Treg response, thereby improving intestinal immunity. These findings can provide a theoretical foundation for utilizing AKG in weaned piglet diets for the regulation of intestinal immune activity through nutrition. Dietary alpha-ketoglutarate can improve the growth performance of piglets. It can alleviate intestinal inflammation induced by lipopolysaccharide through the Th17/Treg immune response signaling pathway and thereby improve intestinal immunity.

Automated summary

This study aimed to investigate the effect of AKG on gut immunity in LPS-challenged piglets by modulating the Th17/Treg immune response signaling pathway. The results showed that dietary AKG supplementation improved growth performance, enhanced ileal morphological structure, and regulated the expression of various immune factors, thereby alleviating LPS-induced intestinal inflammation. Therefore, the addition of AKG to the diet can enhance the growth performance of piglets and improve intestinal immunity.