The increasing prevalence of IgE-mediated cow's milk allergy (CMA) in childhood is a worldwide health concern. There is a growing awareness that the gut microbiome (GM) might play an important role in CMA development. Therefore, treatment with probiotics and prebiotics has gained popularity. This systematic review provides an overview of the alterations of the GM, metabolome, and immune response in CMA children and animal models, including post-treatment modifications. MEDLINE, PubMed, Scopus, and Web of Science were searched for studies on GM in CMA-diagnosed children, published before 1 March 2023. A total of 21 articles (13 on children and 8 on animal models) were included. The studies suggest that the GM, characterized by an enrichment of the Clostridia class and reductions in the Lactobacillales order and Bifidobacterium genus, is associated with CMA in early life. Additionally, reduced levels of short-chain fatty acids (SCFAs) and altered amino acid metabolism were reported in CMA children. Commonly used probiotic strains belong to the Bifidobacterium and Lactobacillus genera. However, only Bifidobacterium levels were consistently upregulated after the intervention, while alterations of other bacteria taxa remain inconclusive. These interventions appear to contribute to the restoration of SCFAs and amino acid metabolism balance. Mouse models indicate that these interventions tend to restore the T_h2/T_h1 balance, increase the T_reg response, and/or silence the overall pro- and anti-inflammatory cytokine response. Overall, this systematic review highlights the need for multi-omics-related research in CMA children to gain a mechanistic understanding of this disease and to develop effective treatments and preventive strategies.

中文翻译：

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当前对儿童牛奶过敏的见解：微生物组、代谢组和免疫反应——系统评价

儿童时期 IgE 介导的牛奶过敏 (CMA) 的患病率不断上升，这是一个全球性的健康问题。人们越来越认识到肠道微生物组 (GM) 可能在 CMA 发展中发挥重要作用。因此，益生菌和益生元的治疗越来越受欢迎。本系统综述概述了 CMA 儿童和动物模型中 GM、代谢组和免疫反应的变化，包括治疗后的修改。在 MEDLINE、PubMed、Scopus 和 Web of Science 上检索了 2023 年 3 月 1 日之前发表的关于 CMA 诊断儿童的 GM 研究。共纳入 21 篇文章（13 篇关于儿童，8 篇关于动物模型）。研究表明，以梭状芽孢杆菌类丰富、乳杆菌目和双歧杆菌属减少为特征的 GM与生命早期的 CMA 相关。此外，据报道，CMA 儿童的短链脂肪酸 (SCFA) 水平降低，氨基酸代谢改变。常用的益生菌菌株属于双歧杆菌属和乳杆菌属。然而，干预后只有双歧杆菌水平持续上调，而其他细菌类群的变化仍不确定。这些干预措施似乎有助于恢复 SCFA 和氨基酸代谢平衡。小鼠模型表明，这些干预措施往往会恢复 T _h 2/T _h 1 平衡，增加 T _reg反应，和/或沉默整体促炎和抗炎细胞因子反应。总体而言，本系统综述强调需要对 CMA 儿童进行多组学相关研究，以获得对该疾病的机制了解并制定有效的治疗和预防策略。