Dietary intervention with sialylated lactulose affects the immunomodulatory activities of mice

Four sialylated lactuloses [N-acetylneuraminic acid-α2,3-lactulose (Neu5Acα2,3lactulose), N-acetylneuraminic acid-α2,6-lactulose (Neu5Acα2,6lactulose), deaminoneuraminc acid-α2,3-lactulose (Kdnα2,3lactulose), and deaminoneuraminc acid-α-2,6-lactulose (Kdnα2,6lactulose)] were reported to modulate the immunity of mice. The influences of cytokine expression, cell immunity, humoral immunity, and nonspecific immunity were investigated in our study using several techniques. Analysis via ELISA showed that cytokine expression was induced by sialylated lactulose treatment consistently in the serum and spleen. Among the 4 tested sialylated lactuloses, Neu5Acα2,6lactulose performed the best, simultaneously and appropriately promoting the expression of proinflammatory and anti-inflammatory factors in the serum and spleen. Kdnα2,3lactulose showed the best antioxidant activity according to detection of the activity of superoxide dismutase, myeloperoxidase, peroxidase, and alkaline phosphatase. Flow cytometry revealed that only Kdnα2,3lactulose significantly boosted the CD3⁺ T lymphocyte ratio similarly to that of lactulose. Analysis of the hemolysin content to characterize humoral immunity revealed that Kdnα2,3lactulose notably increased hemolysin content compared with that in the control group. To evaluate the nonspecific immune effects of the 4 sialylated lactuloses, a fluorescence microsphere phagocytosis assay was used to analyze the phagocytosis of macrophages. Kdnα2,3lactulose still performed the best in enhancing the phagocytosis of macrophages, showing markedly increased phagocytic percentage and phagocytic index values compared with those in the control and lactulose groups. Comparing the differences of these 4 sialylated lactuloses in affecting immunity in mice revealed that Kdnα2,3lactulose had the best overall performance in influencing cytokine expression, cell immunity, humoral immunity, and nonspecific immunity. This study provides critical support for use of sialylated lactuloses as potential immunomodulators in foods.