Maternal Fiber-rich Diet Promotes Early-life Intestinal Development in Offspring Through Milk-derived Extracellular Vesicles Carrying MiR-146a-5p

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2024 Feb 16

PMID 38365722

Authors

Dongdong Lu

Yisi Liu

Luyuan Kang

Xiangyu Zhang

Jie Hu

Hao Ye

Bingxu Huang

Yujun Wu

Jinbiao Zhao

Zhaolai Dai

Junjun Wang

Dandan Han

Affiliations

Soon will be listed here.

Abstract

Backgrounds: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs.

Results: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development.

Conclusion: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-β-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.

Citing Articles

Milk-Derived Extracellular Vesicles: A Novel Perspective on Comparative Therapeutics and Targeted Nanocarrier Application.

Barathan M, Ng S, Lokanathan Y, Ng M, Law J Vaccines (Basel). 2024; 12(11).

PMID: 39591185 PMC: 11599128. DOI: 10.3390/vaccines12111282.

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