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Human breast milk exosomes attenuate intestinal damage

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Abstract

Background

Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given pasteurized donor milk when HBM is unavailable. However, pasteurization can disrupt its components. This study investigates the effects of both raw and pasteurized HBM-derived exosomes on intestinal inflammation.

Methods

HBM exosomes were isolated and characterized by positive CD63 and negative calnexin markers from western blot, nanoparticle tracking analysis and transmission electron microscopy. Mouse intestine organoids were established and treated with exosomes from raw or pasteurized HBM in healthy and injury conditions. Following ethical approval (#44032), mice pups were randomly assigned to (1) breastfed control; (2) NEC; (3) NEC receiving raw HBM exosomes; (4) NEC receiving pasteurized HBM exosomes. NEC was induced by hypoxia, gavage feeding and lipopolysaccharide (LPS). Ileum was evaluated. Data were analyzed using one-way ANOVA with Bonferroni post-test.

Results

Both raw and pasteurized HBM exosomes decreased inflammation in hypoxia and LPS-treated organoids compared to control. In vivo, NEC-induced mucosal injury, inflammation and mucous production were improved by raw and pasteurized HBM-derived exosomes.

Conclusions

Exosomes derived from raw and pasteurized HBM equally reduced intestinal damage. Exosome administration in clinical practice requires further investigation.

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Funding

Dr. Agostino Pierro was funded by Canadian Institutes of Health Research (CIHR) Foundation Grant (Grant number 353857) and the endowment of the Robert M. Filler Chair of Surgery.

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Author notes

  1. Hiromu Miyake and Carol Lee contributed equally to this study.

Authors and Affiliations

  1. Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, 1526-555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Hiromu Miyake, Carol Lee, Sinobol Chusilp, Manvi Bhalla, Bo Li, Shogo Seo & Agostino Pierro

  2. Translational Medicine Program, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Hiromu Miyake, Carol Lee, Sinobol Chusilp, Manvi Bhalla, Bo Li, Michael Pitino, Shogo Seo, Deborah L. O’Connor & Agostino Pierro

  3. Department of Pediatric Surgery, Shizuoka Children’s Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 4208660, Japan

    Hiromu Miyake

  4. Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Sinobol Chusilp

  5. Department of Nutritional Sciences, University of Toronto, 1 King College Circle, Toronto, ON, M5S18, Canada

    Michael Pitino & Deborah L. O’Connor

Authors
  1. Hiromu Miyake
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  2. Carol Lee
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  3. Sinobol Chusilp
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  4. Manvi Bhalla
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  7. Shogo Seo
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  8. Deborah L. O’Connor
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  9. Agostino Pierro
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Contributions

HM, CL, SC, and MB: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript. MP, BL, SS, and DO: collection and/or assembly of data, data analysis and interpretation, and final approval of manuscript. AP: conception and design, financial support, and final approval of manuscript.

Corresponding author

Correspondence to Agostino Pierro.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Care Protocol of the Hospital for Sick Children at which the studies were conducted (Animal Care Committee AUP #44032). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Miyake, H., Lee, C., Chusilp, S. et al. Human breast milk exosomes attenuate intestinal damage. Pediatr Surg Int 36, 155–163 (2020). https://doi.org/10.1007/s00383-019-04599-7

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  • DOI: https://doi.org/10.1007/s00383-019-04599-7

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