Abstract：
BACKGROUND: The pathological mechanism of the gastrointestinal forms of food allergies is less understood in comparison to other clinical phenotypes, such as asthma and anaphylaxis Importantly, high-IgE levels are a poor prognostic factor in gastrointestinal allergies.
METHODS: This study investigated how high-IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock-in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed.
RESULTS: Ovalbumin-sensitized and egg-white diet-fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N-tau-methylhistamine and 2,3-butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non-sensitized and egg-white diet-fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome-for example Akkermansia with lysophosphatidylserine-were detected.
CONCLUSIONS: Our results suggest that high-IgE levels alter intestinal and systemic levels of endogenous and microbiota-associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases.
METHODS: This study investigated how high-IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock-in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed.
RESULTS: Ovalbumin-sensitized and egg-white diet-fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N-tau-methylhistamine and 2,3-butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non-sensitized and egg-white diet-fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome-for example Akkermansia with lysophosphatidylserine-were detected.
CONCLUSIONS: Our results suggest that high-IgE levels alter intestinal and systemic levels of endogenous and microbiota-associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases.
摘要：
背景：与其他临床表型相比，对胃肠道形式食物过敏的病理机制了解较少，如哮喘和过敏反应重要的是，高IgE水平是胃肠道过敏的不良预后因素.
方法：这项研究调查了高IgE水平如何影响过敏性肠炎（AE）中肠道炎症和代谢组的发展，使用表达高水平IgE的IgE敲入(IgEki)小鼠。此外,分析了代谢组改变与肠道微生物组的相关性。
结果：卵清蛋白致敏和蛋清饮食喂养（OVA/EW）的BALB/cWT小鼠出现中度AE，而OVA/EWIgEki小鼠诱导更严重的肠道炎症，嗜酸性粒细胞积累增强。非靶向代谢组学检测到N-tau-甲基组胺和2,3-丁二醇水平升高,OVA/EWIgEki小鼠粪便和/或血清中丁酸水平降低，在属水平上伴随着梭状芽胞杆菌减少和乳杆菌增加。非致敏和蛋清饮食喂养（NC/EW）WT小鼠没有表现出任何AE迹象，而NC/EWIgEki小鼠出现边缘程度的AE。与NC/EWWT小鼠相比，溶血磷脂水平提高，在NC/EWIgEki小鼠的血清和粪便样品中检测到鞘氨醇和鞘氨醇。此外,检测到代谢组改变与肠道微生物组的若干关联,例如Akkermansia与溶血磷脂酰丝氨酸.
结论：我们的结果表明，在实验性AE中，高IgE水平会改变肠道和全身内源性和微生物群相关代谢物的水平。这项研究有助于加深对AE发生的分子机制的认识，并为推进过敏性疾病的诊断和治疗策略提供线索。
方法：这项研究调查了高IgE水平如何影响过敏性肠炎（AE）中肠道炎症和代谢组的发展，使用表达高水平IgE的IgE敲入(IgEki)小鼠。此外,分析了代谢组改变与肠道微生物组的相关性。
结果：卵清蛋白致敏和蛋清饮食喂养（OVA/EW）的BALB/cWT小鼠出现中度AE，而OVA/EWIgEki小鼠诱导更严重的肠道炎症，嗜酸性粒细胞积累增强。非靶向代谢组学检测到N-tau-甲基组胺和2,3-丁二醇水平升高,OVA/EWIgEki小鼠粪便和/或血清中丁酸水平降低，在属水平上伴随着梭状芽胞杆菌减少和乳杆菌增加。非致敏和蛋清饮食喂养（NC/EW）WT小鼠没有表现出任何AE迹象，而NC/EWIgEki小鼠出现边缘程度的AE。与NC/EWWT小鼠相比，溶血磷脂水平提高，在NC/EWIgEki小鼠的血清和粪便样品中检测到鞘氨醇和鞘氨醇。此外,检测到代谢组改变与肠道微生物组的若干关联,例如Akkermansia与溶血磷脂酰丝氨酸.
结论：我们的结果表明，在实验性AE中，高IgE水平会改变肠道和全身内源性和微生物群相关代谢物的水平。这项研究有助于加深对AE发生的分子机制的认识，并为推进过敏性疾病的诊断和治疗策略提供线索。
