Preventive and controlling effects of N-acetylneuraminic acid in regulating glucose and lipid metabolism disorders via the gut-liver axis in high-fat diet mice

A high-fat diet may disrupt sialic acid homeostasis indirectly by altering the gut microbiota and metabolic pathways. Sialic acid interventions have immune-regulatory effects and can improve gut health, but their impact on glucose and lipid metabolism disorders, both before and after obesity induced by a high-fat diet, remains unclear. This study used two models: a preventive experiment (intervention during high-fat diet feeding) and a control experiment (intervention after obesity induction). Each model consisted of a blank control group, a high-fat diet control group, and three N-acetylneuraminic acid (Neu5Ac) intervention groups (low, medium, and high doses), with 12 mice per group. The results showed that both intervention models effectively improved glucose tolerance, and reduced insulin levels, although no significant dose–response relationship was observed. Omics analysis revealed that the intervention increased the abundance of gut microbiota associated with energy metabolism and affected energy metabolism, immune response, and oxidative stress-related signaling pathways in the liver and colon. In the control experiment, inflammation marker levels correlated with improvements in the gut microbiota. Furthermore, the intervention significantly altered the abundance of microbiota linked to glycosylation signaling and metabolic regulation. These findings suggest that Neu5Ac intervention improves gut microbiota structure and function, stabilizes glycan structures, and reduces immune-inflammatory signaling in the gut and liver, thereby lowering systemic inflammation. This helps prevent and control glucose and lipid metabolism disorders induced by a high-fat diet. Notably, the intervention showed stronger effects after obesity had developed due to the high-fat diet.