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口服免疫治疗和低聚果糖治疗牛奶过敏小鼠后微生物群落结构和代谢的改变。

Altered microbial community structure and metabolism in cow's milk allergic mice treated with oral immunotherapy and fructo-oligosaccharides.

机构信息

Utrecht Institute for Pharmaceutical Sciences, Department of Pharmacology, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands.

Immunology Platform, Danone Nutricia Research, Uppsalalaan 12, 3584 CT Utrecht, the Netherlands.

出版信息

Benef Microbes. 2020 Feb 19;11(1):19-32. doi: 10.3920/BM2019.0024. Epub 2019 Dec 17.

Abstract

Previously, we showed enhanced efficacy of oral immunotherapy (OIT) using fructo-oligosaccharides (FOS, prebiotics) added to the diet of cow's milk allergic mice indicated by a reduction in clinical symptoms and mast cell degranulation. Prebiotics are fermented by gut bacteria, affecting both bacterial composition and availability of metabolites (i.e. short-chain fatty acids (SCFA)). It is thus far unknown which microbial alterations are involved in successful outcomes of OIT with prebiotic supplementation for the treatment of food allergy. To explore potential changes in the microbiota composition and availability of SCFA induced by OIT+FOS. C3H/HeOuJ mice were sensitised and received OIT with or without a FOS supplemented diet. After three weeks, faecal samples were collected to analyse gut microbiota composition using 16S rRNA sequencing. SCFA concentrations were determined in cecum content. FOS supplementation in sensitised mice changed the overall microbial community structure in faecal samples compared to sensitised mice fed the control diet (=0.03). In contrast, a high level of resemblance in bacterial community structure was observed between the non-sensitised control mice and the OIT+FOS treated mice. OIT mice showed an increased relative abundance of the dysbiosis-associated phylum Proteobacteria compared to the OIT+FOS mice. FOS supplementation increased the relative abundance of genus (), putative butyrate-producing bacteria. OIT+FOS reduced the abundances of the genera's unclassified (, putative pro-inflammatory bacteria) and unclassified () compared to sensitised controls and increased the abundance of (, putative beneficial bacteria) compared to FOS. OIT+FOS mice had increased butyric acid and propionic acid concentrations. OIT+FOS induced a microbial profile closely linked to non-allergic mice and increased concentrations of butyric acid and propionic acid. Future research should confirm whether there is a causal relationship between microbial modulation and the reduction in acute allergic symptoms induced by OIT+FOS.

摘要

先前,我们发现通过在饮食中添加低聚果糖(FOS,益生元)可增强牛奶过敏小鼠口服免疫治疗(OIT)的疗效,表现在临床症状和肥大细胞脱颗粒减少。益生元被肠道细菌发酵,影响细菌组成和代谢物(即短链脂肪酸(SCFA))的可用性。迄今为止,尚不清楚补充益生元的 OIT 治疗食物过敏成功的结果涉及哪些微生物改变。为了探索 OIT+FOS 治疗引起的微生物组成和 SCFA 可用性的潜在变化。C3H/HeOuJ 小鼠致敏后接受 OIT 和/或添加 FOS 的饮食治疗。3 周后,收集粪便样本,用 16S rRNA 测序分析肠道微生物组成。测定盲肠内容物中 SCFA 浓度。与接受对照饮食的致敏小鼠相比,FOS 补充剂改变了致敏小鼠粪便样本中的整体微生物群落结构(=0.03)。相比之下,非致敏对照小鼠和 OIT+FOS 治疗小鼠的细菌群落结构具有高度相似性。与 OIT+FOS 小鼠相比,OIT 小鼠的失调相关门变形菌的相对丰度增加。FOS 补充剂增加了假定产生丁酸盐的细菌属的相对丰度。与致敏对照相比,OIT+FOS 降低了未分类属的丰度(、假定的促炎细菌)和未分类属的丰度(、假定的有益细菌),并增加了丰度(、假定的有益细菌)与 FOS 相比,。OIT+FOS 小鼠的丁酸和丙酸浓度增加。OIT+FOS 诱导的微生物谱与非过敏小鼠密切相关,并增加了丁酸和丙酸的浓度。未来的研究应证实微生物调节与 OIT+FOS 诱导的急性过敏症状减少之间是否存在因果关系。

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