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Volume 12
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Article

Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy

by
Ching-Min Tang
1,
Gigin Lin
2,3,
Meng-Han Chiang
3,
Kuo-Wei Yeh
1,
Jing-Long Huang
4,
Kuan-Wen Su
5,
Ming-Han Tsai
5,
Man-Chin Hua
5,
Sui-Ling Liao
5,
Shen-Hao Lai
1 and
Chih-Yung Chiu
1,3,*
1
Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan
2
Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan
3
Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
4
Department of Pediatrics, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan
5
Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Metabolites 2022, 12(2), 127; https://doi.org/10.3390/metabo12020127
Submission received: 26 December 2021 / Revised: 27 January 2022 / Accepted: 27 January 2022 / Published: 28 January 2022
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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Abstract

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, n = 33) and formula feeding (EFF, n = 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 1H-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 (p < 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.
Keywords: breastfeeding; formula feeding; milk sensitization; metabolomics; urine breastfeeding; formula feeding; milk sensitization; metabolomics; urine

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MDPI and ACS Style

Tang, C.-M.; Lin, G.; Chiang, M.-H.; Yeh, K.-W.; Huang, J.-L.; Su, K.-W.; Tsai, M.-H.; Hua, M.-C.; Liao, S.-L.; Lai, S.-H.; et al. Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy. Metabolites 2022, 12, 127. https://doi.org/10.3390/metabo12020127

AMA Style

Tang C-M, Lin G, Chiang M-H, Yeh K-W, Huang J-L, Su K-W, Tsai M-H, Hua M-C, Liao S-L, Lai S-H, et al. Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy. Metabolites. 2022; 12(2):127. https://doi.org/10.3390/metabo12020127

Chicago/Turabian Style

Tang, Ching-Min, Gigin Lin, Meng-Han Chiang, Kuo-Wei Yeh, Jing-Long Huang, Kuan-Wen Su, Ming-Han Tsai, Man-Chin Hua, Sui-Ling Liao, Shen-Hao Lai, and et al. 2022. "Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy" Metabolites 12, no. 2: 127. https://doi.org/10.3390/metabo12020127

APA Style

Tang, C.-M., Lin, G., Chiang, M.-H., Yeh, K.-W., Huang, J.-L., Su, K.-W., Tsai, M.-H., Hua, M.-C., Liao, S.-L., Lai, S.-H., & Chiu, C.-Y. (2022). Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy. Metabolites, 12(2), 127. https://doi.org/10.3390/metabo12020127

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