Potential Effects of Three Forms of Sialic Acid on Intestinal Health in Obese Mice Fed With a High‐Fat Diet

ABSTRACT The intestine, a critical barrier against environmental threats, is vulnerable to damage from high‐fat diets (HFD), which disrupt its multilayered structure, increase permeability, trigger inflammation, and elevate metabolic disease risks. This study focuses on the role of the gut–immune axis in the development of obesity, particularly the influence of sialic acid on it. By establishing a HFD‐induced obesity mouse model, we investigated and compared the effects of three forms of sialic acid (N‐acetylneuraminic acid [Neu5Ac], 3ʹ‐sialyllactose [3ʹ‐SL], and fresh stewed edible bird's nest [EBN]) in counteracting the damage caused by an HFD to the mouse intestine. The study found that sialic acid intervention can improve chronic inflammation and metabolic imbalance in HFD‐induced obese mice, which is related to its protective effect on the intestinal mucus barrier and changes in intestinal microbiota and their metabolites. Notably, under the same intervention duration and with equivalent doses of sialic acid, bound sialic acids (3ʹ‐SL and EBN) more effectively increased serum sialic acid levels, improved colonic immune signaling pathways, and reduced serum inflammatory factor levels. These findings suggest that bound sialic acid possesses higher utilization efficiency and provides stronger protection against HFD‐induced chronic inflammation damage to the intestinal. In addition to sialic acid, EBN contains substantial amounts of protein, which is likely responsible for its distinct gut microbiota structure compared to Neu5Ac and 3ʹ‐SL, as well as its superior ability to improve glycolipid metabolism homeostasis. Future studies should further validate the specific contribution of edible bird's nest protein.