健康婴儿体内有可防止食物过敏的肠道菌

Healthy infants harbor intestinal bacteria that protect against food allergy

Feehley et al. nature medicine(2019)

DOI 10.1038/s41591-018-0324-z 

现今西方社会中，有越来越多人对食物过敏。21世纪的生活方式，包括滥用抗生素、饮食内容改变、较高的剖腹产率和配方奶喂养率，使肠道菌群发生改变，这些都是食物过敏机率上升的原因。人类生命早期微生物群的改变可能更加有害。

本研究通过将健康或牛奶过敏（CMA）婴儿的粪便接种到无菌小鼠，研究共生菌调节人类对食物过敏的机制。

Abstract

There has been a striking generational increase in life-threatening food allergies in Westernized societies. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow’s milk allergic (CMA) infants. We found that germ-free mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow’s milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transciptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy. 

关键词：食物过敏，肠道菌群，粪厌氧棒状菌，粪菌移植

研究对象：无菌小鼠（n=3）;4名健康婴儿粪便接种的无菌小鼠（n=18）和4名牛奶过敏婴儿粪便接种的无菌小鼠（n=18）。

实验方法：无菌小鼠和接受健康或牛奶过敏的婴儿微生物群的小鼠使用β-乳球蛋白 (BLG) 和粘膜霍乱毒素致敏，以研究共生菌是否能在防止牛奶过敏原β-乳球蛋白 (BLG) 过敏反应中的因果关系。

检测方法：上皮细胞分离法、组织病理学分析以及16S rRNA、qPCR肠道微生物检测。

研究结果：

1. 健康婴儿粪便接种的无菌小鼠，对牛奶过敏原的过敏反应有保护作用;

2. 通过检测细菌组成的差异可以分辨出健康和牛奶过敏的小鼠，健康和牛奶过敏接种的小鼠回肠上皮出现独特的转录组特征;

3. 一种梭菌属即厌氧棒杆菌（Anaerostipes caccae）可防止食物过敏反应;

4. 无任何细菌定植的无菌小鼠，对食物过敏反应有高度敏感性，这是由于核心体温下降（图1a）和BLG特异性IgE和IgG1的产生（图1b，c）所致;

5. 牛奶过敏的定植小鼠产生的BLG特异性IgE（图1b）、IgG1（图1c）和小鼠肥大细胞蛋白酶-1（MMCPT-1）（图1d）与健康的定植小鼠相比有更高血清浓度。

6. 所有接受健康婴儿肠道菌群的小鼠都没有发生过敏反应。接受母乳喂养健康婴儿的粪便定植的小鼠不受BLG过敏反应的影响。

7. 分析回肠差异性表达基因和菌群OTU的关系，结合单一定植实验，鉴定出产生丁酸的梭菌属粪厌氧棒状菌对牛奶过敏起保护作用

结论：肠道菌群对于调节食物抗原的过敏反应至关重要，调节菌群的干预措施可用于治疗食物过敏。

Fig. 1 | Transfer of healthy, but not CMA, infants’ microbiota protects against an allergic response to food. a, Change in core body temperature at indicated time points following first challenge with BLG in germ-free mice and in mice colonized with feces from each of eight donors (four healthy, four CMA; see Supplementary Table 1) that had been sensitized with BLG plus cholera toxin; n = 42 CMA, 31 healthy and 24 germ-free mice, with 4–12 mice for each of the eight donors, collected from two independent experiments. b–d, Serum BLG-specific IgE (b), BLG-specific IgG1 (c), and mMCPT-1 (d) from mice in a. For a, circles represent mean, and error bars represent s.e.m. For b–d, circles represent individual mice, and bars represent mean + s.e.m. Linear mixed-effect models were used to compare groups in a–d with the BH-FDR method for multiple testing correction. *P < 0.05, **P < 0.01, ***P < 0.001. 

图1. 移植健康但非牛奶过敏的婴儿微生物群可防止食物的过敏反应。A,无细菌小鼠和8名受试者（4名健康，4名牛奶过敏）粪便移植的小鼠,经BLG加霍乱毒素致敏,在第一次过敏发生后指定时间点的核心体温变化;牛奶过敏小鼠（n=42）,健康小鼠（n=31）和无细菌小鼠（n=24）。b-d,血清BLG特异性IgE（b）、BLG特异性IgG1（c）MMCPT-1（d）。*p<0.05，**p<0.01，***p<0.001。

Fig. 2 | Analysis of fecal samples from eight human infant donors reveals taxonomic signatures that correlate with allergic phenotype.

图2. 对8名人类婴儿供体粪便样本的分析揭示了与过敏表型相关的分类特征。

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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