Single-cell transcriptomics reveals that human milk feeding shapes neonatal immune cell interleukin signaling pathways in a nonrandomized clinical trial

作者：Michael L. Salinas, Bharath Kumar Mulakala, Laurie A. Davidson, James J. Cai, Sharon M. Donovan, Robert S. Chapkin, Laxmi Yeruva · 发表于：American Journal of Clinical Nutrition · 年份：2025 · DOI：10.1016/j.ajcnut.2025.04.024 · 被引用次数：7 · 研究领域：Infant Nutrition and Health、Breastfeeding Practices and Influences、Birth, Development, and Health

BACKGROUND: Several studies have indicated the benefits of human milk feeding to infants however, mechanisms behind positive health outcomes have not been investigated. OBJECTIVES: The study aimed to characterize circulating immune cell subpopulation gene expression in human milk-fed (HMF) compared with cow milk formula-fed (FF) infants using single-cell transcriptomics. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy HMF (n = 6), and FF (n = 3) infants who were 3-3.5 mo old and enrolled in a nonrandomized clinical trial. Single-cell RNA sequencing was used to generate a PBMC atlas and evaluate gene expression in immune cell subsets. Differential expression analysis was performed on each cell type independently after clustering the cells by similar marker gene expression using the scGEAToolbox. Differentially expressed genes were subjected to pathway analyses using an online functional enrichment analysis program. RESULTS: The relative abundance (%) of T and B lymphocytes, natural killer (NK) cells, and plasmacytoid dendritic cells were similar, whereas monocytes were higher in FF infants than in HMF infants (22.6 ± 10.7 compared with 8.3 ± 5.6; P = 0.0314). In addition, innate and adaptive immune cells from FF infants exhibited a higher activation state compared with HMF infants. We identified 16 distinct cell subsets from the major immune cell types: 3 monocyte subsets, 4 NK subsets, 2 B cell subsets, and 7 T cell subsets. Transcriptional prof...