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Front Immunol. 2019 Oct 25;10:2543. doi: 10.3389/fimmu.2019.02543. eCollection 2019.

Breast Milk-Derived Extracellular Vesicles Enriched in Exosomes From Mothers With Type 1 Diabetes Contain Aberrant Levels of microRNAs.

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Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Pediatrics E, Copenhagen Diabetes Research Center (CPH-DIRECT), Herlev and Gentofte Hospital, Herlev, Denmark.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Faculty of Health Sciences, Institute of Public Health, CSS, University of Copenhagen, Copenhagen, Denmark.
Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
Center for Pregnant Women With Diabetes, Rigshospitalet, Copenhagen, Denmark.
Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
Department of Obstetrics, Herlev Hospital, Herlev, Denmark.


The breast milk plays a crucial role in shaping the initial intestinal microbiota and mucosal immunity of the infant. Interestingly, breastfeeding has proven to be protective against the early onset of immune-mediated diseases including type 1 diabetes. Studies have shown that exosomes from human breast milk are enriched in immune-modulating miRNAs suggesting that exosomal miRNAs (exomiRs) transferred to the infant could play a critical role in the development of the infant's immune system. We extracted exomiRs from breast milk of 52 lactating mothers (26 mothers with type 1 diabetes and 26 healthy mothers), to identify any differences in the exomiR content between the two groups. Small RNA-sequencing was performed to identify known and novel miRNAs in both groups. A total of 631 exomiRs were detected by small RNA sequencing including immune-related miRNAs such as hsa-let-7c, hsa-miR-21, hsa-miR-34a, hsa-miR-146b, and hsa-miR-200b. In addition, ~200 novel miRNAs were identified in both type 1 diabetes and control samples. Among the known miRNAs, nine exomiR's were found differentially expressed in mothers with type 1 diabetes compared to healthy mothers. The highly up-regulated miRNAs, hsa-miR-4497, and hsa-miR-3178, increased lipopolysaccharide-induced expression and secretion of tumor necrosis factor α (TNFα) in human monocytes. The up-regulated miRNA target genes were significantly enriched for longevity-regulating pathways and FoxO signaling. Our findings suggest a role of breast milk-derived exomiRs in modulating the infant's immune system.


Type 1 diabetes; breast milk; exomiRs; exosomes; miRNAs

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