The 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.

Microorganisms that colonize the intestine communicate with the host in various ways and affect gut function and health. Extracellular vesicles (EVs), especially their encapsulated microRNAs (miRNAs), participate in the complex and precise regulation of microbiota–host interactions in the gut. These roles make miRNAs critically important for the prevention, diagnosis, and treatment of intestinal diseases. Here, we review the current knowledge on how different sources of EVs and miRNAs, including those from diets, gut microbes, and hosts, maintain gut microbial homeostasis and improve the intestinal barrier and immune function. We further highlight the roles of EVs and miRNAs in intestinal diseases, including diarrhea, inflammatory bowel disease, and colorectal cancer, thus providing a perspective for the application of EVs and miRNAs in these diseases.