Tang Ching-Min, Lin Gigin, Chiang Meng-Han, Yeh Kuo-Wei, Huang Jing-Long, Su Kuan-Wen, Tsai Ming-Han, Hua Man-Chin, Liao Sui-Ling, Lai Shen-Hao, Chiu Chih-Yung
Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan.
Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan.
Metabolites. 2022 Jan 28;12(2):127. doi: 10.3390/metabo12020127.
Early exposure to formula milk increases the likelihood of cow's milk sensitization and food allergies in the later childhood. However, the underlying mechanisms are multifactorial and unclear. Fifty-five children from a follow-up birth cohort study were grouped into exclusive breastfeeding (EBF, = 33) and formula feeding (EFF, = 22) in the first six months of life. Urinary metabolites were longitudinally assessed and analyzed at 6 months, 1, and 2 years of age using H-nuclear magnetic resonance (NMR) spectroscopy. Integrated analysis of metabolic profiling associated with formula feeding and milk sensitization related to IgE reactions was also investigated. Twenty-two metabolites were significantly obtained in the EFF set at age 0.5, whereas nine metabolites were predominantly obtained in the milk sensitization set at age 1. A subsequent analysis of metabolic change from 6 months to age 1 identified eight metabolites, including 3-methyl-2-oxovaleric acid, glutarate, lysine, N-phenylacetylglycine, N,N-dimethylglycine, 3-indoxysulfate, 2-oxoglutaric acid, and pantothenate associated with formula feeding and milk sensitization with same trend variation. Among them, 3-indoxysulfate, N-phenylacetylglycine, and N,N-dimethylglycine were gut microbial-derived without IgE association. By contrast, 3-methyl-2-oxovaleric acid, glutarate, and lysine were IgE related associated with formula feeding contributing to milk sensitization ( < 0.05). Longitudinal urinary metabolomic analysis provides molecular insight into the mechanism of formula feeding associated with milk sensitization. Gut microbial-derived metabolites associated with formula feeding and IgE associated metabolites related to branched-chain amino acid metabolism play roles in developing sensitization and allergic symptoms in response to formula feeding.
早期接触配方奶会增加儿童后期对牛奶过敏和食物过敏的可能性。然而，其潜在机制是多因素的且尚不清楚。在一项出生队列随访研究中，55名儿童在出生后的前六个月被分为纯母乳喂养组（EBF，n = 33）和配方奶喂养组（EFF，n = 22）。使用氢核磁共振（NMR）光谱法对6个月、1岁和2岁时的尿液代谢物进行纵向评估和分析。还研究了与配方奶喂养相关的代谢谱以及与IgE反应相关的牛奶致敏的综合分析。在0.5岁的EFF组中显著获得了22种代谢物，而在1岁的牛奶致敏组中主要获得了9种代谢物。随后对6个月至1岁的代谢变化分析确定了8种代谢物，包括3 - 甲基 - 2 - 氧代戊酸、戊二酸、赖氨酸、N - 苯乙酰甘氨酸、N，N - 二甲基甘氨酸、3 - 吲哚硫酸盐、2 - 氧代戊二酸和泛酸盐，它们与配方奶喂养和牛奶致敏具有相同的趋势变化。其中，3 - 吲哚硫酸盐、N - 苯乙酰甘氨酸和N，N - 二甲基甘氨酸是肠道微生物衍生的，与IgE无关。相比之下，3 - 甲基 - 2 - 氧代戊酸、戊二酸和赖氨酸与配方奶喂养相关且与IgE有关，促成了牛奶致敏（P < 0.05）。纵向尿液代谢组学分析为配方奶喂养与牛奶致敏相关的机制提供了分子层面的见解。与配方奶喂养相关的肠道微生物衍生代谢物以及与支链氨基酸代谢相关的IgE相关代谢物在因配方奶喂养而产生的致敏和过敏症状发展中起作用。
