2′-Fucosyllactose and 3′-Sialyllactose Reduce Mortality in Neonatal Enteroaggregative <i>Escherichia coli</i> Infection by Improving the Construction of Intestinal Mucosal Immunity

Human milk oligosaccharides could prevent pathogenic bacterial infections in neonates; however, direct in vivo anti-infection evidence was still lacking. Here, we systematically evaluated the effects of 2'-fucosyllactose (2'-FL) and 3'-sialyllactose (3'-SL) on the structural development and functional maturation in neonates and their defense against enteroaggregative <i>Escherichia coli</i> infection. It was found that supplementation with 2'-FL and 3'-SL improved the resistance of weaned mice to enteroaggregative <i>E. coli</i>. The mechanism related to the promotion of 2'-FL and 3'-SL in the maturation of intestinal mucosal immunity by promoting stem cell differentiation, mucus layer integrity, and tight junction formation. 2'-FL and 3'-SL significantly increased the ratio of Th1 and Treg cells in the lamina propria, contents of short-chain fatty acids, as well as the serum content of IgA. This study lays a theoretical basis for the application of 2'-FL and 3'-SL in infant formula, as well as the development of intestinal health products.