Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p
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 mat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-02344-4 |
| _version_ | 1797273389279215616 |
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| author | Dongdong Lu Yisi Liu Luyuan Kang Xiangyu Zhang Jie Hu Hao Ye Bingxu Huang Yujun Wu Jinbiao Zhao Zhaolai Dai Junjun Wang Dandan Han |
| author_facet | Dongdong Lu Yisi Liu Luyuan Kang Xiangyu Zhang Jie Hu Hao Ye Bingxu Huang Yujun Wu Jinbiao Zhao Zhaolai Dai Junjun Wang Dandan Han |
| author_sort | Dongdong Lu |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| first_indexed | 2024-03-07T14:42:42Z |
| format | Article |
| id | doaj.art-6c6e85fcb0da4aa4929245e390c9e96a |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-07T14:42:42Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-6c6e85fcb0da4aa4929245e390c9e96a2024-03-05T20:09:59ZengBMCJournal of Nanobiotechnology1477-31552024-02-0122111910.1186/s12951-024-02344-4Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5pDongdong Lu0Yisi Liu1Luyuan Kang2Xiangyu Zhang3Jie Hu4Hao Ye5Bingxu Huang6Yujun Wu7Jinbiao Zhao8Zhaolai Dai9Junjun Wang10Dandan Han11State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityAdaptation Physiology Group, Wageningen University & ResearchState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural UniversityAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02344-4Maternal dietResistant starchOffspringIntestinal developmentMilk-derived extracellular vesiclesmiR-146a-5p |
| spellingShingle | Dongdong Lu Yisi Liu Luyuan Kang Xiangyu Zhang Jie Hu Hao Ye Bingxu Huang Yujun Wu Jinbiao Zhao Zhaolai Dai Junjun Wang Dandan Han Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p Journal of Nanobiotechnology Maternal diet Resistant starch Offspring Intestinal development Milk-derived extracellular vesicles miR-146a-5p |
| title | Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p |
| title_full | Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p |
| title_fullStr | Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p |
| title_full_unstemmed | Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p |
| title_short | Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p |
| title_sort | maternal fiber rich diet promotes early life intestinal development in offspring through milk derived extracellular vesicles carrying mir 146a 5p |
| topic | Maternal diet Resistant starch Offspring Intestinal development Milk-derived extracellular vesicles miR-146a-5p |
| url | https://doi.org/10.1186/s12951-024-02344-4 |
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