Abstract: Purpose: This study aimed to investigate the alleviating effects of sialic acid (SA) and 3’-sialyllactose (3’-SL) on dextran sulfate sodium (DSS)-induced colitis in mice and to evaluate their influence on the intestinal microbiota structure. Methods: Forty-eight specific pathogen-free (SPF) male C57BL/6 mice (4–5 weeks old) were randomly divided into 4 groups (n = 12/group): a control (CON) group, which received daily intragastric administration of phosphate-buffered saline; a DSS group, which drank water from day 1 to 21 and then drank 0.025 g/mL DSS aqueous solution from day 22 to 29; and a DSS + SA and a DSS + 3’-SL group, which drank water containing 2 mg/mL SA and 2 mg/mL 3’-SL from day 1 to 21 and then 0.025 g/mL DSS aqueous solution, respectively. Body mass, fecal traits and bleeding status of mice were recorded daily from day 22 onwards. On day 29, the mice were anesthetized and sacrificed. Serum, colon tissues and colonic contents were collected for subsequent detection and analysis. Results: Intervention with SA and 3’-SL restored mouse body mass, increased colon length, alleviated edema, and significantly reduced disease activity index (DAI) (P < 0.05). Both SA and 3’-SL upregulated the expression of tight junction proteins and mucins, and decreased the levels of inflammatory factors in the colon and serum. At the phylum level, compared with the DSS group, both SA and 3’-SL upregulated the abundance of Firmicutes and downregulated the abundance of Verrucomicrobiota, with significant differences between groups (P < 0.05). At the species level, the DSS + SA group was enriched with Akkermansia muciniphila, Muribaculum intestinale and Turicibacter sanguinis, while the DSS + 3’-SL group was enriched with A. muciniphila, Monoglobus pectinilyticus, and Lactobacillus murinus. Both SA and 3’-SL alleviated DSS-induced colitis in mice, but there were differences in their mechanisms of action. SA acted directly on the host intestinal barrier and immune regulation, while 3’-SL specifically enriched beneficial bacteria and reshaped intestinal microbial balance through its oligosaccharide structure. Conclusion: The probiotic function of 3’-SL is not entirely dependent on its metabolic product SA, and the two compounds have complementary mechanisms of action. This provides a theoretical basis for the precise nutritional combination of SA and 3’-SL as functional food ingredients.

Key words: sialic acid; 3’-sialyllactose; dextran sulfate sodium; intestinal injury; gut microbiota