Microbiota-Derived Extracellular Vesicles Promote Immunityand Intestinal Maturation in Suckling Rats

Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mucosal surface, such as extracellular membrane vesicles (EVs). The EVs released by the gut microbiota have been extensively studied in cellular and experimental models of human diseases. However, little is known about their in vivo effects in early life, specifically regarding immune and intestinal maturation. This study aimed to investigate the effects of daily administration of EVs from probiotic and commensal E. coli strains in healthy suckling rats during the first 16 days of life. On days 8 and 16, we assessed various intestinal and systemic variables in relation to animal growth, humoral and cellular immunity, epithelial barrier maturation, and intestinal architecture. On day 16, animals given probiotic/microbiota EVs exhibited higher levels of plasma IgG, IgA, and IgM and a greater proportion of Tc, NK, and NKT cells in the spleen. In the small intestine, EVs increased

the villi area and modulated the expression of genes related to immune function, inflammation, and intestinal permeability, shifting towards an anti-inflammatory and barrier protective profile from day 8. In conclusion, interventions involving probiotic/microbiota EVs may represent a safe postbiotic strategy to stimulate immunity and intestinal maturation in early life.