Milk sialyl-oligosaccharides mediate the early colonization of gut commensal microbes in piglets

The suckling period in pigs is a key phase in development for shaping the gut microbiota, which is essential for maintaining biological homeostasis in neonates. In piglets fed sow milk, the gut microbiota comprises predominantly lactobacilli, indicating a host-gut microbiota symbiosis that is influenced by sow milk components. In this study, we sought to elucidate the mechanisms underlying the establishment and maintenance of the gut microbiome in suckling piglets, with a specific focus on the metabolism of sialyl-oligosaccharides by lactobacilli. Based on liquid chromatography-mass spectrometry analysis, we identified 3'-sialyl-lactose (3'SL) as the major oligosaccharide in porcine milk, and microbiome profiling revealed the predominance of Ligilactobacillus salivarius during the suckling period, with a subsequent transition to Limosilactobacillus reuteri dominance post-weaning. Notably, sialic acid metabolism was established to be exclusively attributable to L. salivarius, thereby highlighting the pivotal role of 3'SL in determining species-specific bacterial segregation. L. salivarius was found to metabolize 3'SL when co-cultured with Bacteroides thetaiotaomicron, resulting in a shift in the predominant short-chain fatty acid produced, from lactate to acetate. This metabolic shift, in turn, inhibits the growth of enterotoxigenic Escherichia coli. Furthermore, the comparison of the gut microbiota between suckling piglets and those fed a low-3'SL formula revealed distinct diversity profiles. We accordingly speculate that an absence of sialyl-oligosaccharides in the formula-fed piglets may have restricted the growth of sialic acid-utilizing bacteria such as L. salivarius, thereby leading to a higher abundance of Enterobacteriaceae. Our findings reveal the influence of sialyl-oligosaccharides in promoting microbial diversity and gut homeostasis, thereby highlighting the importance of sialic acid as a key factor in shaping milk-driven microbial colonization during the early stages of piglet development. Video Abstract.