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Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway

Metabolites of probiotics that are beneficial to human health have been isolated from the intestinal tract and natural dairy products. However, many studies on probiotics and prebiotics are limited to the observation of human cohorts and animal phenotypes. The molecular mechanisms by which metabolit...

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Autores principales: Qiao, Zhenyi, Wang, Xiaohua, Wang, Chaoyue, Han, Jin, Qi, Weiwei, Zhang, Huanchang, Liu, Zhenmin, You, Chunping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968858/
https://www.ncbi.nlm.nih.gov/pubmed/35369066
http://dx.doi.org/10.3389/fnut.2022.799053
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author Qiao, Zhenyi
Wang, Xiaohua
Wang, Chaoyue
Han, Jin
Qi, Weiwei
Zhang, Huanchang
Liu, Zhenmin
You, Chunping
author_facet Qiao, Zhenyi
Wang, Xiaohua
Wang, Chaoyue
Han, Jin
Qi, Weiwei
Zhang, Huanchang
Liu, Zhenmin
You, Chunping
author_sort Qiao, Zhenyi
collection PubMed
description Metabolites of probiotics that are beneficial to human health have been isolated from the intestinal tract and natural dairy products. However, many studies on probiotics and prebiotics are limited to the observation of human cohorts and animal phenotypes. The molecular mechanisms by which metabolites of probiotics regulate health are still need further exploration. In this work, we isolated a strain of Lactobacillus Paracasei from human milk samples. We numbered it as Lactobacillus Paracasei BD5115. The mouse model of high-fat diet confirmed that the metabolites of this strain also promotes intestinal epithelial cells (IECs) proliferation. Single-cell sequencing showed that a bZIP transcription factor MAFF was specifically expressed in some IECs. We found that MAFF interacted with MBP1 to regulate the expression of MYC. Analysis of the active components in BD5115 metabolites confirmed that 2-hydroxy-3-methylbutyric acid promotes the expression of the MYC gene. This promotes the proliferation of IECs. Our findings indicate that 2-hydroxy-3-methylbutyric acid regulate MYC gene expression mediated by MAFF/MBP1 interaction. This study not only screened a strain with promoted IECs proliferation, but also discovered a new signal pathway that regulates MYC gene expression.
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spelling pubmed-89688582022-04-01 Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway Qiao, Zhenyi Wang, Xiaohua Wang, Chaoyue Han, Jin Qi, Weiwei Zhang, Huanchang Liu, Zhenmin You, Chunping Front Nutr Nutrition Metabolites of probiotics that are beneficial to human health have been isolated from the intestinal tract and natural dairy products. However, many studies on probiotics and prebiotics are limited to the observation of human cohorts and animal phenotypes. The molecular mechanisms by which metabolites of probiotics regulate health are still need further exploration. In this work, we isolated a strain of Lactobacillus Paracasei from human milk samples. We numbered it as Lactobacillus Paracasei BD5115. The mouse model of high-fat diet confirmed that the metabolites of this strain also promotes intestinal epithelial cells (IECs) proliferation. Single-cell sequencing showed that a bZIP transcription factor MAFF was specifically expressed in some IECs. We found that MAFF interacted with MBP1 to regulate the expression of MYC. Analysis of the active components in BD5115 metabolites confirmed that 2-hydroxy-3-methylbutyric acid promotes the expression of the MYC gene. This promotes the proliferation of IECs. Our findings indicate that 2-hydroxy-3-methylbutyric acid regulate MYC gene expression mediated by MAFF/MBP1 interaction. This study not only screened a strain with promoted IECs proliferation, but also discovered a new signal pathway that regulates MYC gene expression. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8968858/ /pubmed/35369066 http://dx.doi.org/10.3389/fnut.2022.799053 Text en Copyright © 2022 Qiao, Wang, Wang, Han, Qi, Zhang, Liu and You. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Qiao, Zhenyi
Wang, Xiaohua
Wang, Chaoyue
Han, Jin
Qi, Weiwei
Zhang, Huanchang
Liu, Zhenmin
You, Chunping
Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title_full Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title_fullStr Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title_full_unstemmed Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title_short Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
title_sort lactobacillus paracasei bd5115-derived 2-hydroxy-3-methylbutyric acid promotes intestinal epithelial cells proliferation by upregulating the myc signaling pathway
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968858/
https://www.ncbi.nlm.nih.gov/pubmed/35369066
http://dx.doi.org/10.3389/fnut.2022.799053
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