Functional shifts in immune composition follow lactation stage in human milk - Summary - MDSpire

Functional shifts in immune composition follow lactation stage in human milk

  • By

  • Jia Ming Low

  • Melissa Shu Feng Ng

  • Chen-Shi Lin

  • Jian-Zhou Cui

  • Meera K. Shenoy

  • Sheau Yng Lim

  • Lu-Yi Ng

  • Si Min Lang

  • Wai-Chung Ong

  • Tamanna Ferdous

  • Rashi Gupta

  • Tanusya Murali Murali

  • Isabelle Tan

  • Karishma Sachaphibulkij

  • Yung-Seng Lee

  • Paul A MacAry

  • June 24, 2026

  • 0 min

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Objective:

To determine if the milk immune microenvironment exhibits stage-associated changes across different lactation phases.

Approach:
  • Study Design: Multi-modal profiling using single-cell RNA sequencing, high-dimensional flow cytometry, and soluble protein assays on paired maternal blood and milk samples collected during colostrum, transitional, and mature milk stages.
Key Findings:
  • Human milk contains transcriptionally distinct immune and epithelial cellular populations compared to maternal peripheral blood.
  • Colostrum showed greater neutrophil enrichment with antimicrobial-associated transcriptional programs, including degranulation- and NETosis-associated signatures.
  • Later lactation stages exhibited stronger effector-memory-associated T-cell transcriptional signatures.
  • Stage-associated differences in soluble immune mediator profiles were observed, with early recruitment-associated cytokines declining and IL-7 increasing in mature milk.
Interpretation:

Human milk undergoes substantial stage-associated remodeling of cellular and soluble immune components across lactation.

Limitations:
  • Limited longitudinal paired analyses of fresh human milk and matched maternal blood across lactation stages.
  • The study cohort consisted of a small number of donors.
Conclusion:

Further studies will be required to determine the functional significance of these stage-associated immune features.

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