# Changes in and relationships between human milk oligosaccharides and microRNAs in milk-derived extracellular vesicles during the first 4 months of lactation

**Authors:** Mai Morozumi, Hirohisa Izumi, Muneya Tsuda, Fuka Tabata, Hirohiko Nakamura, Kazuhiro Miyaji

PMC · DOI: 10.3389/fnut.2025.1694093 · Frontiers in Nutrition · 2025-12-22

## TL;DR

This study examines how human milk oligosaccharides and microRNAs in milk-derived extracellular vesicles change during the first 4 months of lactation in Japanese women.

## Contribution

The study reveals a potential relationship between HMO concentrations and miRNAs in milk-derived extracellular vesicles during lactation.

## Key findings

- Most HMO concentrations significantly decreased over 4 months of lactation.
- 3′-sialyllactose and lacto-N-fucopentaose III were inversely correlated with top 20 miRNAs in MEVs.
- Secretor status influenced miRNA abundance in MEVs during early lactation.

## Abstract

Human milk oligosaccharides (HMOs) exert beneficial effects on the gut microbiota, enhance resistance to infections, support immune development, and contribute to brain/cognitive development. Milk-derived extracellular vesicles (MEVs) contain a high abundance of immunity- and development-related microRNAs (miRNAs). These components are abundant in breast milk. In the case of HMOs, the composition varies due to factors such as lactation stages, geographic location, ethnicity, genetics, and the environment. The composition of HMOs is significantly influenced by the genetic status of two key genes: FUT2 (Secretor gene) and FUT3 (Lewis gene). In this study, we broadly categorized them as secretors or non-secretors.

We investigated the changes in the concentrations of HMOs and MEVs during 4 months of lactation in Japanese women and explored the relationship between HMOs and miRNAs present in MEVs.

The concentrations of most HMOs significantly decreased over time. The number of MEVs did not change significantly over the study period. Interestingly, 3′-sialyllactose and lacto-N-fucopentaose III were inversely correlated with many of the top 20 most abundant miRNAs. Moreover, miRNAs in MEVs, which are associated with immunity and development, were more abundant in secretors than in non-secretors during early lactation. Several HMOs were detected in MEVs.

This study enabled a detailed characterization of changes in HMOs and MEVs in the breast milk of Japanese women throughout the course of the first 4 months of lactation. A potential association between the concentrations of HMOs and miRNAs was also observed, suggesting that these components might influence each other. These findings are significant for promoting healthy infant development and growth, as well as for improving infant formula composition.

## Linked entities

- **Genes:** FUT2 (fucosyltransferase 2 (H blood group)) [NCBI Gene 2524], FUT3 (fucosyltransferase 3 (Lewis blood group)) [NCBI Gene 2525]

## Full-text entities

- **Genes:** FUT3 (fucosyltransferase 3 (Lewis blood group)) [NCBI Gene 2525] {aka CD174, FT3B, FucT-III, LE, Les}, FUT2 (fucosyltransferase 2 (H blood group)) [NCBI Gene 2524] {aka B12QTL1, SE, SEC2, Se2, sej}
- **Diseases:** infections (MESH:D007239)
- **Chemicals:** HMOs (-), oligosaccharides (MESH:D009844), 3'-sialyllactose (MESH:C421467)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12766977/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12766977/full.md

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Source: https://tomesphere.com/paper/PMC12766977