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种族与食物过敏的关联受生命第一年肠道微生物群发展的影响。

Ethnicity Associations With Food Sensitization Are Mediated by Gut Microbiota Development in the First Year of Life.

机构信息

HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China; Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

HKU-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China.

出版信息

Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016. Epub 2021 Mar 16.

DOI:10.1053/j.gastro.2021.03.016
PMID:33741316
Abstract

BACKGROUND AND AIMS

Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children.

METHODS

In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted.

RESULTS

Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13-7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75-22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization.

CONCLUSIONS

This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.

摘要

背景与目的

越来越多的证据表明,早期肠道微生物群在特应性疾病的发展中起作用,但婴儿期肠道微生物群与食物致敏相关的生态变化仍不清楚。我们旨在描述这些变化,并将其与儿童食物致敏的发展相关联。

方法

在这项观察性研究中,我们使用 16S rRNA 扩增子测序技术,对 1422 名加拿大足月婴儿的 2844 份粪便微生物群进行了特征描述。在 1 岁和 3 岁时通过皮肤点刺试验测量特应性致敏结果。根据社区聚类的纵向变化确定肠道微生物群轨迹与 1 岁和 3 岁时特应性致敏结果之间的关联。最初检查了影响微生物群轨迹的种族和生命早期暴露因素,并进行了事后分析。

结果

确定了 4 种肠道微生物群的发育轨迹,这些轨迹受出生方式的影响,并因种族而异。整个婴儿期一直存在低拟杆菌丰度和高肠杆菌科/拟杆菌科比例的轨迹增加了对食物过敏原(尤其是 3 岁时对花生)的致敏风险,增加了 3 倍(调整后的优势比 [OR] 2.82,95%置信区间 [CI] 1.13-7.01)。如果具有这种轨迹的婴儿出生于亚洲母亲,则对花生过敏的可能性要大得多(调整后的 OR 7.87,95%CI 2.75-22.55)。它的特征是鞘脂代谢缺陷和持续的艰难梭菌定植。重要的是,这种拟杆菌丰度降低的轨迹介导了亚洲种族与食物致敏之间的关联。

结论

本研究记录了婴儿期整个肠道拟杆菌丰度持续降低与儿童时期对花生过敏之间的关联。这是首次表明婴儿肠道微生物群在与种族相关的食物致敏发展中起中介作用。

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