Gut–Mammary Axis-Mediated Improvement of Sialylated Milk Oligosaccharide Synthesis by Polygonatum sibiricum Polysaccharide and Probiotics in Mice with Gestational Metabolic Disorders

Abstract Milk oligosaccharides (MOs) are vital for infant health but vulnerable to gestational metabolic dysfunction. To explore a new microecological intervention strategy, we established a probiotic fermentation platform coupled with a mammary epithelial cell screening model to identify Polygonatum sibiricum polysaccharide (PSP) as a promising candidate. Murine models demonstrated that both PSP monotherapy and synergistic treatment with probiotics significantly mitigated gestational metabolic dysregulation and restored postpartum sialylated MOs. Mechanistically, the combined treatment outperformed single interventions by modulating glycerophospholipid (GPL) and polyunsaturated fatty acid (PUFA) metabolism, mitigating mammary gland mitochondrial dysfunction and ATP deficiency, and significantly upregulating the mRNA expression of sialyltransferase gene ST3GAL1. Notably, ATP restoration improved precursor availability, while ST3GAL1 upregulation promoted terminal sialylation, jointly facilitating sialylated MO biosynthesis. Our findings provide novel insights into how maternal metabolic health governs sialylated MO biosynthesis via the gut–mammary gland axis and propose a synergistic microecological intervention strategy for gestational metabolic disorders.