Comparative effect of sialic acid and 3′‐sialyllactose on fecal microbiota fermentation and prebiotic activity in ETEC‐challenged IPEC‐J2 cells

BACKGROUND: Sialic acid (SA) and 3'-sialyllactose (3'-SL) are potential food supplements, capable of promoting gut health and brain development. Structurally, 3'-SL can be formed by coupling a sialyl moiety to lactose via α-2,3 glycosidic linkages. However, there is currently no conclusive evidence regarding the role of the sialyl moiety in the prebiotic function of 3'-SL or its contribution to the biological activity of 3'-SL itself. RESULTS: This study demonstrated that SA and 3'-SL differentially modulate the gut microbial community structure during in vitro fermentation, selectively promoting the growth of specific microbiota and altering short-chain fatty acid production profiles. Specifically, SA significantly increased acetate levels whereas 3'-SL mainly elevated the production of butyrate. At the cellular level, both compounds consistently strengthened intestinal barrier integrity in IPEC-J2 cells, reduced apoptosis, and alleviated oxidative stress induced by enterotoxigenic Escherichia coli. CONCLUSION: This study highlights the prebiotic potential of SA and 3'-SL in maintaining intestinal homeostasis, an effect likely mediated by their distinct structural properties. © 2025 Society of Chemical Industry.