Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, South Korea.
Pediatr Allergy Immunol. 2023 Aug;34(8):e14003. doi: 10.1111/pai.14003.
Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA.
We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA.
In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid.
Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.
持续性食物过敏（FA）的发病机制尚不清楚。肠道黏膜是食物过敏原的主要暴露途径。然而，目前尚无研究探讨与 FA 持续性相关的肠道代谢物。本研究旨在探讨早期生活中与 FA 发生和持续性相关的肠道代谢物和相关微生物群。
我们通过基于质谱的非靶向代谢组学分析，根据 FA 对婴儿粪便中的代谢物进行了鉴定。进行了胆汁酸代谢物和粪便微生物组的靶向代谢组学分析。通过对 3 月龄婴儿进行 FA 缓解和持续性 FA 分组，评估婴儿期胆汁酸代谢物组成。
在非靶向代谢组学中，FA 组和健康对照组之间的初级胆汁酸生物合成存在显著差异。在胆汁酸靶向代谢组学中，FA 组婴儿肠道中的替代途径合成的胆汁酸代谢物减少，而健康对照组婴儿则没有。与健康对照组和 FA 缓解组相比，持续性 FA 组的替代途径胆汁酸代谢物也有所不同。这些代谢物与蛋清特异性 IgE 水平呈负相关。FA 组肠道梭菌丰度降低，与熊去氧胆酸呈正相关。
肠道替代途径的胆汁酸代谢物可能是儿童早期持续性 FA 的预测生物标志物。这些发现需要在未来的研究中进行复制。
