There has been increased interest in the use of dietary ingredients, including prebiotics such as human-milk oligosaccharides (HMOs), as therapeutic strategies for food allergy. Understanding the mechanisms underlying the beneficial effects of HMOs is important to realizing their therapeutic potential. Here we demonstrate that the HMO, 6'-sialyllactose (6'SL) inhibited chemokine (IL-8 and CCL20) release from T-84 and HT-29 cells stimulated with antigen-antibody complex, TNFα or PGE2 ; an effect that was PPARγ dependent and associated with decreased activity of the transcription factors AP-1 and NFκB. In contrast, 2'-fucosyllactose (2'FL) selectively inhibited CCL20 release in response to antigen antibody complex in a PPARγ independent manner. This study reinforces the concept that structurally different oligosaccharides have distinct biological activities and identifies, for the first time, that the HMOs, 6'SL, and 2'FL, modulate human epithelial cell responses related to allergic disease. These findings encourage further investigation of the therapeutic potential of specific HMOs in food allergy. PRACTICAL APPLICATION This study provides evidence for direct effects of HMOs in addition to their prebiotic role and demonstrates, for the first time, modulation of Ag-IgE complex activation of human epithelial cells that may have important implications for food-allergy. The study also reinforces the concept that structurally different oligosaccharides have distinct biological activities. In determining the composition of infant formula, addition of oligosaccharides with specific structures may provide direct modulation of immune responses and potentially attenuate symptoms or development of food allergy.

中文翻译：

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人乳寡糖减弱抗原抗体复合物诱导的人肠上皮细胞系的趋化因子释放

人们越来越关注使用膳食成分，包括益生元，如人乳寡糖 (HMO)，作为食物过敏的治疗策略。了解 HMO 有益作用的潜在机制对于实现其治疗潜力非常重要。在这里，我们证明了 HMO、6'-唾液酸乳糖 (6'SL) 抑制了由抗原-抗体复合物、TNFα 或 PGE2 刺激的 T-84 和 HT-29 细胞释放趋化因子（IL-8 和 CCL20）；这种效应依赖于 PPARγ，并与转录因子 AP-1 和 NFκB 的活性降低有关。相反，2'-岩藻糖基乳糖 (2'FL) 以不依赖 PPARγ 的方式选择性抑制 CCL20 释放以响应抗原抗体复合物。这项研究强化了结构不同的寡糖具有不同生物活性的概念，并首次确定了 HMO、6'SL 和 2'FL 调节与过敏性疾病相关的人类上皮细胞反应。这些发现鼓励进一步研究特定 HMO 在食物过敏中的治疗潜力。实际应用 本研究提供了 HMO 除了益生元作用之外的直接影响的证据，并首次证明了对人类上皮细胞 Ag-IgE 复合物活化的调节，这可能对食物过敏具有重要意义。该研究还强化了结构不同的寡糖具有不同生物活性的概念。在确定婴儿配方奶粉的成分时，