Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
Allergy. 2019 Jan;74(1):176-185. doi: 10.1111/all.13485. Epub 2018 Oct 18.
Compositional changes in the early-life gut microbiota have been implicated in IgE-associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation.
Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL-10 and FOXP3 mRNA copies were determined using real-time quantitative reverse transcriptase-PCR.
At 8 years of age, 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (r = 0.49 P = 0.02) with the same trend for FOXP3 (r = 0.39 P = 0.08).
We identified both temporal and long-term variation in the differential abundance of specific bacterial genera in children developing IgE-associated allergic disease. Improved dietary interventions aiming at expanding immune-modulatory taxa could be studied for prevention of allergic disease.
生命早期肠道微生物组的组成变化与 IgE 相关的过敏性疾病有关，但缺乏纵向研究。我们研究了从婴儿期到学龄期肠道微生物组的发展与 IgE 相关的过敏性疾病发病之间的关系。在 8 岁时，我们还研究了肠道微生物组与 T 细胞调节之间的关系，这是通过多克隆 T 细胞激活的反应来估计的。
从 93 名儿童的 4、6、13 个月和 8 岁时收集粪便样本。使用 16S rRNA 基因测序对肠道微生物组进行分析。从所有儿童采集外周血，多克隆激活单核细胞。使用实时定量逆转录聚合酶链反应测定 IL-10 和 FOXP3 mRNA 拷贝的水平。
在 8 岁时，21 名儿童被诊断为 IgE 相关过敏性疾病，90%的儿童存在过敏合并症。72 名儿童为非过敏和非致敏。经多次测试校正的统计检验表明，从婴儿期到学龄期，过敏儿童肠道微生物组中厚壁菌门的代表性不足，拟杆菌门、普雷沃氏菌属和粪球菌属的代表性持续不足。过敏 8 岁儿童的肠道微生物组富含双歧杆菌，而乳杆菌属、肠球菌属和lachnospira 属则减少。在过敏的 8 岁儿童中，粪杆菌与 IL-10 mRNA 水平呈正相关(r = 0.49，P = 0.02)，FOXP3 也有同样的趋势(r = 0.39，P = 0.08)。
我们发现，在发展为 IgE 相关过敏性疾病的儿童中，特定细菌属的丰度存在时间和长期变化。可以研究旨在扩大免疫调节类群的改善饮食干预措施，以预防过敏性疾病。
