Evidence map›Paper›PMID 40294751›Full record

Trial reportThe American journal of clinical nutrition2025

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

Michael L Salinas, Bharath Kumar Mulakala, Laurie A Davidson, James J Cai, Sharon M Donovan, Robert S Chapkin, Laxmi Yeruva

Abstract readClinical Trial
In one paragraph

Trial report in The American journal of clinical nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Michael L SalinasDepartment of Nutrition, Texas A&M University, College Station, TX, United States; CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX, United States; Texas A&M AgriLife Institute for Advancing Health Through Agriculture, College Station, TX, United States.
Bharath Kumar MulakalaTexas A&M AgriLife Institute for Advancing Health Through Agriculture, College Station, TX, United States; Microbiome and Metabolism Research Unit, USDA-ARS, SEA, Little Rock, AR, United States; Arkansas Children's Nutrition Center, Little Rock, AR, United States.
Laurie A DavidsonDepartment of Nutrition, Texas A&M University, College Station, TX, United States; CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX, United States.
James J CaiCPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX, United States; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United States; Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, United States.
Sharon M DonovanDepartment of Food Science and Human Nutrition, Personalized Nutrition Initiative, University of Illinois, Urbana, IL, United States.
Robert S ChapkinDepartment of Nutrition, Texas A&M University, College Station, TX, United States; CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX, United States; Texas A&M AgriLife Institute for Advancing Health Through Agriculture, College Station, TX, United States. Electronic address: r-chapkin@tamu.edu.
Laxmi YeruvaMicrobiome and Metabolism Research Unit, USDA-ARS, SEA, Little Rock, AR, United States; Arkansas Children's Nutrition Center, Little Rock, AR, United States. Electronic address: laxmi.yeruva@usda.gov.

Funding

Impact of Emotions on Treatment Decisions About Low-Risk Thyroid CancerK08CA230204 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI PITT, SUSAN C · 2018 to 2023
$1.4M
NCI NIH HHS K08 CA230204
6 · The paper itself

Abstract

backgroundSeveral studies have indicated the benefits of human milk feeding to infants however, mechanisms behind positive health outcomes have not been investigated.

objectivesThe 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.

methodsPeripheral 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.

resultsThe 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 profiles of each peripheral innate and adaptive immune cell subtype varied between HMF and FF infants. Pathway enrichment analysis of cell-specific transcriptional changes within subsets of major cell types revealed that the interleukin (IL)-4/IL-13 signaling pathways were upregulated in FF infants relative to HMF infants.

conclusionsThese findings suggest that human milk downregulates peripheral immune cell cytokine transcriptional signatures linked to allergic inflammation and infection relative to formula feeding.

Indexed as

InterleukinsLeukocytes, MononuclearMilk, HumanSignal TransductionTranscriptomeFemaleHumansInfantInfant FormulaInfant, NewbornMaleMilkSingle-Cell AnalysisInterleukinsallergyhuman milkinfant formulainflammationperipheral blood mononuclear cells

Identifiers

PMID40294751
PMCPMC13639470

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.