Kerperien J, Jeurink P V, Wehkamp T, van der Veer A, van de Kant H J G, Hofman G A, van Esch E C A M, Garssen J, Willemsen L E M, Knippels L M J
Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Pediatr Allergy Immunol. 2014 Dec;25(8):747-54. doi: 10.1111/pai.12311. Epub 2014 Dec 18.
Cow's milk allergy is a common food allergy in childhood and no effective preventive or curative treatment is available. This study aimed at comparing single short-chain galacto- (scGOS), long-chain fructo- (lcFOS) or pectin-derived acidic oligosaccharides (pAOS) and/or mixtures of scGOS/lcFOS (GF) or scGOS/lcFOS/pAOS (GFA) to prevent or treat food allergy.
In the preventive protocol, C3H/HeOuJ mice were fed diets containing single oligosaccharides or mixtures GF or GFA throughout the study protocol. In the treatment protocol, GF or GFA was provided for 4 wk starting after the last sensitization. The allergic skin response and anaphylaxis scores were determined, after oral challenge whey-specific immunoglobulins were measured, and qPCR for T-cell markers and Foxp3 counts using immunohistochemistry were performed on the small intestine and colon.
Only in the preventive setting, the GF or GFA mixture, but not the single oligosaccharides, reduced the allergic skin response and whey-IgG(1) levels in whey-sensitized mice, compared to the control diet. Both GF and GFA increased the number of Foxp3+ cells in the proximal small intestine of whey - compared to sham-sensitized mice. Expression of Th2 and Th17 mRNA markers increased in the middle part of the small intestine of whey-sensitized mice, which was prevented by GF. By contrast, GFA enhanced Tbet (Th1), IL-10 and TGF-β mRNA expression compared to GF which was maintained in the distal small intestine and/or colon.
Dietary supplementation with scGOS/lcFOS or scGOS/lcFOS/pAOS during sensitization, both effectively reduce allergic symptoms but differentially affect mucosal immune activation in whey-sensitized mice.
牛奶过敏是儿童期常见的食物过敏,目前尚无有效的预防或治疗方法。本研究旨在比较单一的短链半乳糖寡糖(scGOS)、长链果寡糖(lcFOS)或果胶衍生的酸性寡糖(pAOS)和/或scGOS/lcFOS混合物(GF)或scGOS/lcFOS/pAOS混合物(GFA)对食物过敏的预防或治疗作用。
在预防方案中,C3H/HeOuJ小鼠在整个研究过程中喂食含有单一寡糖或GF或GFA混合物的饮食。在治疗方案中,在最后一次致敏后开始提供GF或GFA,持续4周。测定过敏皮肤反应和过敏反应评分,口服激发后测量乳清特异性免疫球蛋白,并对小肠和结肠进行T细胞标志物的qPCR检测以及使用免疫组织化学法计数Foxp3。
仅在预防组中,与对照饮食相比,GF或GFA混合物而非单一寡糖可降低乳清致敏小鼠的过敏皮肤反应和乳清IgG1水平。与假致敏小鼠相比,GF和GFA均可增加乳清致敏小鼠近端小肠中Foxp3+细胞的数量。乳清致敏小鼠小肠中部Th2和Th17 mRNA标志物的表达增加,而GF可预防这种增加。相比之下,与GF相比,GFA增强了Tbet(Th1)、IL-10和TGF-β mRNA的表达,且在远端小肠和/或结肠中维持这种增强。
在致敏期间饮食补充scGOS/lcFOS或scGOS/lcFOS/pAOS均可有效减轻过敏症状,但对乳清致敏小鼠的黏膜免疫激活有不同影响。