丁酸盐与2'-岩藻糖基乳糖（2'FL）和3-岩藻糖基乳糖（3FL）的作用相互影响，以调节卵清蛋白诱导的免疫激活，并且在鸡蛋过敏的临床前模型中，2'FL可降低黏膜肥大细胞的激活。
Butyrate interacts with the effects of 2'FL and 3FL to modulate ovalbumin-induced immune activation, and 2'FL lowers mucosal mast cell activation in a preclinical model for hen's egg allergy.
作者信息
Zuurveld M, Diks M A P, Kiliaan P C J, Garssen J, Folkerts G, Van't Land B, Willemsen L E M
机构信息
Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
Danone Nutricia Research B.V, Utrecht, Netherlands.
出版信息
Front Nutr. 2023 Dec 19;10:1305833. doi: 10.3389/fnut.2023.1305833. eCollection 2023.
BACKGROUND
Early life provides a window of opportunity to prevent allergic diseases. With a prevalence of 0.5-2% in infants, hen's egg allergy is one of the most common food allergies. The immunomodulatory effects of human milk oligosaccharides (HMOs), 2'-fucosyllactose (2'FL), and 3-fucosyllactose (3FL) were studied in an mucosal immune model and an murine model for hen's egg (ovalbumin) allergy.
METHODS
Intestinal epithelial cell (IEC)/dendritic cell (DC) and DC/T cell cocultures were used to expose IECs to ovalbumin (OVA) in an mucosal immune model. The effects of epithelial pre-incubation with 0.1% 2'FL or 3FL and/or 0.5 mM butyrate were studied. Three- to four-weeks-old female C3H/HeOuJ mice were fed AIN93G diets containing 0.1-0.5% 2'FL or 3FL 2 weeks before and during OVA sensitization and challenge. Allergic symptoms and systemic and local immune parameters were assessed.
RESULTS
Exposing IECs to butyrate left the IEC/DC/T cell cross-talk unaffected, while 2'FL and 3FL showed differential immunomodulatory effects. In 3FL exposed IEC-DC-T cells, the secretion of IFNγ and IL10 was enhanced. This was observed upon pre-incubation of IECs with 2'FL and butyrate as well, but not 2'FL alone. The presence of butyrate did not affect OVA activation, but when combined with 3FL, an increase in IL6 release from DCs was observed ( < 0.001). OVA allergic mice receiving 0.5% 3FL diet had a lower %Th2 cells in MLNs, but the humoral response was unaltered compared to control mice. OVA-allergic mice receiving 0.1 or 0.5% 2'FL diets had lower serum levels of OVA-IgG2a ( < 0.05) or the mast cell marker mMCP1, in association with increased concentration of cecal short-chain fatty acids (SCFAs) ( < 0.05).
CONCLUSION
butyrate exposure promotes the development of a downstream type 1 and regulatory response observed after 2'FL exposure. 2'FL and 3FL differentially modulate ovalbumin-induced mucosal inflammation predominantly independent of butyrate. Mice receiving dietary 3FL during ovalbumin sensitization and challenge had lowered Th2 activation while the frequency of Treg cells was enhanced. By contrast, 2'FL improved the humoral immune response and suppressed mast cell activation in association with increased SCFAs production in the murine model for hen's egg allergy.
背景
生命早期为预防过敏性疾病提供了一个机会窗口。鸡蛋过敏在婴儿中的患病率为0.5 - 2%，是最常见的食物过敏之一。在黏膜免疫模型和鸡蛋（卵清蛋白）过敏的小鼠模型中研究了人乳寡糖（HMOs）、2'-岩藻糖基乳糖（2'FL）和3-岩藻糖基乳糖（3FL）的免疫调节作用。
方法
在黏膜免疫模型中，使用肠上皮细胞（IEC）/树突状细胞（DC）和DC/T细胞共培养，使IEC暴露于卵清蛋白（OVA）。研究了用0.1% 2'FL或3FL和/或0.5 mM丁酸盐对上皮细胞进行预孵育的效果。在OVA致敏和激发前2周及期间，给3至4周龄的雌性C3H/HeOuJ小鼠喂食含0.1 - 0.5% 2'FL或3FL的AIN93G饮食。评估过敏症状以及全身和局部免疫参数。
结果
使IEC暴露于丁酸盐对IEC/DC/T细胞的相互作用没有影响，而2'FL和3FL显示出不同的免疫调节作用。在暴露于3FL的IEC-DC-T细胞中，IFNγ和IL10的分泌增加。在用2'FL和丁酸盐对IEC进行预孵育时也观察到了这种情况，但单独使用2'FL时未观察到。丁酸盐的存在不影响OVA的激活，但与3FL联合使用时，观察到DC释放的IL6增加（P < 0.001）。接受0.5% 3FL饮食的OVA过敏小鼠，其肠系膜淋巴结中Th2细胞的百分比降低，但与对照小鼠相比，体液反应未改变。接受0.1%或0.5% 2'FL饮食的OVA过敏小鼠，其OVA-IgG2a血清水平较低（P < 0.05）或肥大细胞标志物mMCP1较低，同时盲肠短链脂肪酸（SCFAs）浓度增加（P < 0.05）。
结论
丁酸盐暴露促进了在2'FL暴露后观察到的下游1型和调节性反应的发展。2'FL和3FL主要独立于丁酸盐对卵清蛋白诱导的黏膜炎症进行不同的调节。在OVA致敏和激发期间接受饮食3FL的小鼠，其Th2激活降低，而调节性T细胞的频率增加。相比之下，在鸡蛋过敏的小鼠模型中，2'FL改善了体液免疫反应并抑制了肥大细胞激活，同时SCFAs的产生增加。
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