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

Abstract

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 Th17/Treg balance pathway. A 2 × 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). Alpha-ketoglutarate 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-1β, tumor necrosis factor-α, 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.

α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction

“…LPS challenge also decreased ileal villus height while upregulating concentrations of proinflammatory cytokines such as IL-6 and TNFα. Alterations to villus height and cytokine profile were mitigated by the addition of 1.0% AKG to the diet [ 69 ]. Carp fed low-protein diets supplemented with 0.4% AKG exhibited reduced concentrations of IL-1b and IL-6α compared to carp on low-protein diets without AKG supplementation [ 70 ].…”

“…IL-10 is an important anti-inflammatory cytokine that suppresses the transcription of proinflammatory genes, and its knockout in mice results in the spontaneous development of intestinal inflammation resembling CD [ 71 , 72 ]. AKG supplementation restored intestinal IL-10 concentrations in piglets challenged with LPS [ 69 ]. In LPS-challenged piglets, dietary AKG promoted regulatory T cell differentiation and suppressed Th17 cell differentiation in the intestine [ 69 ].…”

“…AKG supplementation restored intestinal IL-10 concentrations in piglets challenged with LPS [ 69 ]. In LPS-challenged piglets, dietary AKG promoted regulatory T cell differentiation and suppressed Th17 cell differentiation in the intestine [ 69 ]. Aged mice receiving AKG showed higher concentrations of IL-10 secreted by splenic T cells [ 64 ].…”