Gellan gum-sialoglycan conjugates: a mucin mimic for alleviating inflammation in Caco-2 cells and modulating gut microbiota in the elderly

The sialylation of intestinal mucins plays a crucial role in maintaining intestinal homeostasis and shaping the gut microbiota. This study aims to develop a mucin-like polymer to modulate the intestinal microbiota in the elderly individuals. We synthesized functionalized conjugates using sialic acid monomer, 3'-sialyllactose, and Gellan gum, resulting in a series of GG-sialoglycan conjugates with diverse glycan chain lengths and terminal structures. The sialic acid contents of GG-EDA-Sia, GG-EDA-SL, GG-HAD-Sia, and GG-HAD-SL were 28.48 %, 29.78 %, 23.45 and 41.58 %, respectively. These conjugates exhibited anti-digestion effects. In addition, they demonstrated favorable biocompatibility and exhibited notable anti-inflammatory properties. In vitro fermentation experiments using fecal bacteria from elderly individuals revealed that GG-sialoglycan conjugates enhanced the proliferation of beneficial bacteria such as Lactobacillus, Bifidobacterium, and Blautia, while simultaneously suppressing pathogens like Escherichia-Shigella. It is worth noting that GG-sialoglycan conjugates containing 3'-sialyllactose exhibited superior prebiotic activity compared to those with sialic acid monomer. In summary, our findings strongly support the promising potential of functional sialic acid-based macromolecular glycan conjugates as a novel strategy to improve aging-related intestinal health.