Shibata Ryohei, Nakanishi Yumiko, Suda Wataru, Nakano Taiji, Sato Noriko, Inaba Yosuke, Kawasaki Yohei, Hattori Masahira, Shimojo Naoki, Ohno Hiroshi
Laboratorie for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan; Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba City, Japan.
Laboratorie for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
J Allergy Clin Immunol. 2025 Mar;155(3):932-946. doi: 10.1016/j.jaci.2024.10.029. Epub 2024 Dec 16.
Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations.
We sought to characterize gut microbiota in children using an enterotyping approach and determine the association of gut microbiota and the enterotypes with the development of FS and FA.
We combined gut microbiome and fecal short-chain fatty acid data from 2 longitudinal birth-cohort studies in Japan, clustered the microbiome data from children who were 1 week to 7 years old and their mothers and identified enterotypes. We also determined the associations of gut microbiota and enterotypes with risks of developing FS and FA across the 2 studies using multivariable regression models.
Data from the 2563 microbiomes identified 6 enterotypes. More gut bacteria (eg, Bifidobacterium) in 1-month-old children showed significant relationships with the development of FS and FA than in 1-week-old children. Enterotypes at 1 month old consisted of Bacteroides-dominant, Klebsiella-dominant, and Bifidobacterium-dominant enterotypes. Bifidobacterium-dominant enterotypes with the highest fecal propionate concentration had the lowest risks of developing FS and FA, especially of hen egg white sensitization. Bifidobacterium-dominant enterotypes had lower risks at 2 years old in one study (vs Bacteroides-dominant enterotype, adjusted odds ratio [adjOR]: 0.10, 95% CI: 0.01-0.78; vs Klebsiella-dominant enterotype, adjOR: 0.10, 95% CI: 0.01-0.77) and at 9 months old in the other study (vs Bacteroides-dominant enterotype, adjOR: 0.33, 95% CI: 0.11-0.91).
In these birth-cohort studies, gut microbiome clustering identified distinct neonatal enterotypes with differential risks of developing FS and FA.
食物致敏（FS）在婴儿早期出现，是随后发生食物过敏（FA）的一个风险因素。最近的证据表明肠道微生物群与FS和FA之间存在关联。然而，关于新生儿肠道微生物群在这些表现的病理生物学中的作用知之甚少。
我们试图采用肠型分类法对儿童肠道微生物群进行特征描述，并确定肠道微生物群和肠型与FS和FA发生之间的关联。
我们整合了日本两项纵向出生队列研究中的肠道微生物组和粪便短链脂肪酸数据，对1周龄至7岁儿童及其母亲的微生物组数据进行聚类，并确定肠型。我们还使用多变量回归模型在这两项研究中确定了肠道微生物群和肠型与发生FS和FA风险之间的关联。
来自2563个微生物组的数据确定了6种肠型。与1周龄儿童相比，1月龄儿童中更多的肠道细菌（如双歧杆菌）与FS和FA的发生呈显著相关。1月龄时的肠型包括拟杆菌主导型、克雷伯菌主导型和双歧杆菌主导型。粪便丙酸浓度最高的双歧杆菌主导型肠型发生FS和FA的风险最低，尤其是蛋清致敏。在一项研究中，双歧杆菌主导型肠型在2岁时风险较低（与拟杆菌主导型肠型相比，调整后的优势比[adjOR]：0.10，95%置信区间：0.01-0.78；与克雷伯菌主导型肠型相比，adjOR：0.10，95%置信区间：0.01-0.77），在另一项研究中，在9月龄时风险较低（与拟杆菌主导型肠型相比，adjOR：0.33，95%置信区间：0.11-0.91）。
在这些出生队列研究中，肠道微生物组聚类确定了不同的新生儿肠型，其发生FS和FA的风险不同。
