Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets

Simple SummaryAs a nonprotein amino acid, γ-aminobutyric acid (GABA) plays a vital role in intestinal function. This study aimed to investigate the underlying mechanisms by which GABA affects intestinal health in piglets. The results showed that GABA significantly improved growth performance, reduced diarrhea, and mitigated inflammation. Additionally, microbiota profiling revealed enhanced diversity and changes in the composition of ileal bacteria and fungi. Metabolomic and transcriptomic analyses suggested that dietary supplementation with GABA could affect several pathways related to nutrient digestion and absorption. We further confirmed that GABA increased the activities of lipase and trypsin, as well as elevated the expression of tight junction proteins. Therefore, we propose that dietary 80 mg/kg GABA supplementation may enhance nutrient digestion and absorption, thereby improving intestinal function in weanling piglets.AbstractThe nonprotein amino acid γ-aminobutyric acid (GABA) can enhance intestinal function in piglets; however, the mechanisms involved are not yet fully understood. To explore the effects of GABA and its underlying mechanisms, weanling piglets were randomly assigned to three groups, receiving either a basal diet or a basal diet supplemented with GABA (80 mg/kg or 120 mg/kg). The results demonstrated that dietary GABA improved growth performance and reduced diarrhea incidence (p< 0.05). Additionally, GABA supplementation decreased the serum and intestinal levels of pro-inflammatory cytokines (p< 0.05), and improved intestinal morphology. Multi-omics analyses were employed to explore the alterations caused by GABA supplementation and elucidate the related mechanisms. Microbiota profiling revealed improved beta-diversity and changes in the composition of ileal bacteria and fungi. Amino acid metabolism, lipid metabolism, and digestive processes were primarily enriched in the GABA group according to metabolomics analysis. A transcriptome analysis showed significant enrichment in ion transmembrane transport and nutrition absorption and digestion pathways in the ileum. Furthermore, increased lipase and trypsin activity, along with the elevated expression of tight junction proteins confirmed the beneficial effects of GABA on intestinal nutrient metabolism and barrier function. In conclusion, dietary 80 mg/kg GABA supplementation improved nutrient digestion and absorption and intestinal function in weanling piglets.