儿童过敏8年，其肠道菌群有哪些变化？

Temporal and long-term gut microbiota variation in allergic disease: A prospective study from infancy to school age

Sjödin et al. Allergy (2017)

DOI 10.1111/all.13485

粘膜表面微生物暴露对免疫发育和调节至关重要。在出生后阶段，胃肠道微生物的逐步定植与先天免疫系统和适应性免疫系统的成熟并行。越来越多的人认识到，这种定植过程对于促进免疫系统的发育至关重要。

尽管湿疹、呼吸道过敏性疾病和食物过敏的患病率随年龄的不同而不同，但过敏性疾病合并症很常见，并且具有共同的危险因素——胃肠道细菌缺失。特定细菌分类群的减少与湿疹和哮喘的发展有关，最近还发现与食物过敏有关。

本研究是一项纵向前瞻性研究，旨在研究从婴儿期到学龄期肠道微生物群的发展、组成和多样性，以及与出生后8年内发生过敏性疾病相关的肠道微生物群。

同时，本研究还检测了肠道微生物组成及其与多克隆T细胞活化反应的关系，作为T细胞调节的指标。

Background: Compositional changes of the early life gut microbiota have been implicated in IgE-associated allergic disease 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. 

Methods: Stool samples were collected from 93 children at 4, 6 and 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. 

Results: At 8 years of age 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were non-allergic and non-sensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella and Coprococcus in allergic compared to non-allergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcusand Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (rs=0.49, Padj=0.02) with the same trend for FOXP3 (rs=0.39, Padj=0.08). 

Conclusions: 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.

关键词：过敏、多样性、肠道定植、微生物群、T细胞应答

研究对象：瑞典的93名儿童。

入组标准：

1. 来源于一项随机安慰剂对照试验（NCT 00894816，研究益生菌对过敏性疾病的以及预防作用）；

2. 有出生后4个月、6个月、13个月及8岁时的粪便样本。

实验方法： 

1. 4-13个月大的，先前没有过敏症状的婴儿，随机分为两组：

   每天摄入含益生菌副干酪乳杆菌F19（乳酸杆菌F19）1 x 10^8 的婴儿谷类食物（n=89）；

   另外一组每天摄入不含益生菌的婴儿谷类食物（n=90）;

2. 父母使用日记卡报告了湿疹、气喘、哮喘、食物过敏和药物的症状和体征。研究人员阅读日记卡，每月使用一份有结构的过敏性疾病症状和体征问卷对父母进行了访问;

3. 干预阶段结束于2001-2003年；2009-2011年8-9岁时进行了临床随访；

4. 8岁时进行过敏症状诊断。

检测方法：宏基因组测序，16S rRNA 基因测序等

研究结果：

1. 8岁时，21名儿童被诊断出IgE相关的过敏性疾病，90%共患多种过敏性疾病；72名儿童没有过敏性疾病；

2. 20名儿童对空气中的过敏原敏感，13名儿童对食物过敏原敏感；14名儿童有特应性湿疹，14名儿童有过敏性鼻炎，4名儿童有哮喘，5名儿童有食物过敏。

3. 过敏患儿的粪便菌群中瘤胃球菌属（Ruminococcus）短暂减少，而拟杆菌属（Bacteroides）、普雷沃氏菌属（Prevotella）、粪球菌属（Coprococcus）长期减少；

4. 8岁时，过敏患儿的粪便菌群中双歧杆菌属（Bifidobacterium）富集，乳杆菌属（Lactobacillus）、肠球菌属（Enterococcus）、毛螺菌属（Lachnospira）缺失；

5. 抽取所有儿童的外周血，激活外周血单核细胞，发现柔嫩梭菌属（Faecalibacterium）与IL-10的mRNA及FOXP3水平相关

结论：

本文确定了患有IgE 相关性过敏性疾病的儿童中特异性菌群丰度的短期和长期变化。未来应改良饮食干预手段，以增加调节免疫的菌群，预防过敏性疾病。

Figure 4. Relative abundance of bacterial taxa within the Firmicutes phylum according to intake of the probiotic Lactobacillus F19 in infancy at 4, 6, 13 months and 8 years of age. There was a higher relative abundance of Lactobacillus in the probiotic group at 6 months (Padj<0.05), but not at the other samplings.

图4. 婴儿期4、6、13个月和8岁时厚壁菌门内细菌类群的相对丰度。6个月时，益生菌组的乳酸菌相对丰度较高，但其他样本的乳酸菌相对丰度不高。

知几未来研究院正在搭建一个“疾病-肠道菌群”知识库。

你可以在公众号对话框回复“IBD”或“肠易激综合征”，查看与疾病相关的菌群；

也可以回复“双歧杆菌”或“Hp”，查看与细菌相关的疾病。

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