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

Ching Min Tang, 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, Chih Yung Chiu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations

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 using1 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 microbialderived 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.

Original languageEnglish
Article number127
JournalMetabolites
Volume12
Issue number2
DOIs
StatePublished - 02 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Breastfeeding
  • Formula feeding
  • Metabolomics
  • Milk sensitization
  • Urine

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