Breast Milk-Derived Extracellular Vesicle Mirnas are Associated with Maternal Asthma and Atopy

Abstract

Background: Breast milk-derived extracellular vesicle (EV) miRNAs may program child health outcomes associated with maternal asthma and atopy. The authors investigated associations between maternal asthma/atopy and EV miRNAs in the Programming of Intergenerational Stress Mechanisms cohort. Methods: Breast milk-derived EV miRNAs collected 6.1 ± 5.9 weeks postnatally (n = 80 mothers) were profiled using the TaqMan OpenArray Human MicroRNA Panel. The authors assessed associations using adjusted robust regression. Results: Nine EV miRNAs were associated with asthma during pregnancy (a priori criteria: nominal p < 0.05; |B_regression| >0.2). miR-1290 was associated with asthma and atopy during pregnancy (p < 0.05; |B_regression| >0.2). Enriched Kyoto Encyclopedia of Genes and Genomes pathways included TGF-β signaling and extracellular matrix–receptor interaction (false discovery rate <0.05). Conclusion: In this study, maternal asthma and atopy were associated with breast milk-derived EV miRNAs. Additional studies are needed to understand whether EV miRNAs have direct effects on infant and child health.

Plain language summary

Maternal asthma is associated with child health outcomes, although the biological mechanisms involved are not fully understood. miRNAs are small molecules involved in regulating gene expression. miRNAs packaged into membrane-bound particles called extracellular vesicles (EVs) are present in human breast milk and may pass from mother to infant to signal which genes to translate into proteins. This study investigated the extent to which maternal asthma and atopy influenced levels of 130 EV miRNAs measured in breast milk. Nine EV miRNAs were associated with maternal asthma during pregnancy, and one EV miRNA was associated with maternal atopy. miRNAs associated with asthma target genes in pathways related to asthma; however, future research is needed to determine whether changes in breast milk-derived EV miRNAs impact child health.

Keywords::

• asthma
• atopy
• breast milk
• extracellular vesicles
• miRNA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0090

Author contributions

AK Bozack developed the data analysis plan, analyzed and visualized data and drafted the manuscript. E Colicino developed the data analysis plan and reviewed and edited the manuscript. RS Rodosthenous developed the data analysis plan and reviewed and edited the manuscript. TR Bloomquist was involved in data collection and reviewed and edited the manuscript. AA Baccarelli reviewed and edited the manuscript. RO Wright reviewed and edited the manuscript. RJ Wright was involved in developing study methodology and funding acquisition and reviewed and edited the manuscript. AG Lee conceptualized the project, was involved in developing study methodology and funding acquisition and reviewed and edited the manuscript. All authors read and approved the final manuscript.

Acknowledgments

The authors would like to acknowledge the study staff and participants, without whom this work would not have been possible. The authors thank P Wang in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai for her expertise in analytical methods.

Financial&competing interests disclosure

The Programming of Intergenerational Stress Mechanisms cohort has been supported by US NIH grants R01 HL095606, R01 HL114396 and R01 ES030302 to RJ Wright (principal investigator). During preparation of this manuscript, AG Lee was supported by US NIH grants R01 MD013310 and K23 HL135349. Analysis of extracellular vesicle miRNAs was supported by US NIH pilot grant P30 ES023515 to AG Lee and RJ Wright. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The institutional review board at the Icahn School of Medicine at Mount Sinai approved the study protocol. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Data are available upon reasonable request to the corresponding author and appropriate permission from the Programming of Intergenerational Stress Mechanisms study team as well as institutional review board approval. R code for all analyses is available at the study’s GitHub repository (https://github.com/annebozack/microRNA_maternalAsthma).

Additional information

Funding

The Programming of Intergenerational Stress Mechanisms cohort has been supported by US National Institutes of Health(NIH) grants R01 HL095606, R01 HL114396 and R01 ES030302 to RJ Wright (principal investigator). During preparation of this manuscript, AG Lee was supported by US National Institutes of Health (NIH) grants R01 MD013310 and K23 HL135349. Analysis of extracellular vesicle miRNAs was supported by US National Institutes of Health (NIH) pilot grant P30 ES023515 to AG Lee and RJ Wright. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.