Mechanisms by which sialic acid influences the gut microbiota and its metabolism in infants, based on an in vitro spatiotemporal dynamic digestion model

Background Sialic acid (SA), chemically known as N ‐acetylneuraminic acid (NANA), is a key bioactive component of breast milk. It reaches the infant's colon largely intact for utilization by the gut microbiota; however, its dynamic fermentation and specific regulatory mechanisms remain unclear. Results An in vitro biomimetic gut digestion system (BGR‐7) was employed to investigate systematically the effects of SA on the infant gut microbiota and its metabolism. The results indicated that SA effectively enhanced the richness of the gut microbiota and optimized community structure. At the phylum level, SA selectively enriched Bacillota, Fusobacteriota, Cyanobacteriota and Thermodesulfobacteriota, while suppressing Pseudomonadota, Bacteroidota, and Actinomycetota. At the genus level, SA promoted the proliferation of beneficial bacteria such as Lactococcus, Enterococcus, Bacteroides and Bifidobacterium , whilst inhibiting potentially pathogenic bacteria such as Streptococcus, Escherichia‐Shigella, Citrobacter , and Enterobacter . Analysis of gut gases revealed that SA regulates the production of CO 2 , H 2 , volatile organic compounds (VOCs) and H 2 S, maintaining the physiological homeostasis of metabolic products. Significant correlation was observed between microbial composition and gaseous metabolites. Metabolomics analysis identified a total of 248 differentially abundant metabolites (78 up‐regulated and 170 down‐regulated), primarily enriched in pathways such as fatty acid metabolism and inositol phosphate metabolism. Conclusion Sialic acid exerts a synergistic protective effect in the infant gut by regulating the structure of the microbial community, gas metabolism, and metabolic networks with multiple targets. This study provides experimental evidence and theoretical guidance for the application of SA in infant nutritional interventions and the development of functional foods.