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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Main Authors: Zhenyi Qiao, Xiaohua Wang, Chaoyue Wang, Jin Han, Weiwei Qi, Huanchang Zhang, Zhenmin Liu, Chunping You
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2022.799053/full
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author Zhenyi Qiao
Zhenyi Qiao
Xiaohua Wang
Chaoyue Wang
Chaoyue Wang
Jin Han
Weiwei Qi
Huanchang Zhang
Zhenmin Liu
Chunping You
author_facet Zhenyi Qiao
Zhenyi Qiao
Xiaohua Wang
Chaoyue Wang
Chaoyue Wang
Jin Han
Weiwei Qi
Huanchang Zhang
Zhenmin Liu
Chunping You
author_sort Zhenyi Qiao
collection DOAJ
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 doaj.art-ef61a343ea2c415086965c3a1120621a2022-12-21T23:42:04ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-03-01910.3389/fnut.2022.799053799053Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling PathwayZhenyi Qiao0Zhenyi Qiao1Xiaohua Wang2Chaoyue Wang3Chaoyue Wang4Jin Han5Weiwei Qi6Huanchang Zhang7Zhenmin Liu8Chunping You9State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Postdoctoral Workstation of Bright Dairy–Shanghai Jiao Tong University, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaCollege of Food Science and Technology, Shanghai Ocean University, Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaShanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaMetabolites 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.https://www.frontiersin.org/articles/10.3389/fnut.2022.799053/full2-hydroxy-3-methylbutyric acidtranscription factorcolitis-associated cancer (CAC)Lactobacillus paracasei BD5115intestinal epithelial cells proliferation
spellingShingle Zhenyi Qiao
Zhenyi Qiao
Xiaohua Wang
Chaoyue Wang
Chaoyue Wang
Jin Han
Weiwei Qi
Huanchang Zhang
Zhenmin Liu
Chunping You
Lactobacillus paracasei BD5115-Derived 2-Hydroxy-3-Methylbutyric Acid Promotes Intestinal Epithelial Cells Proliferation by Upregulating the MYC Signaling Pathway
Frontiers in Nutrition
2-hydroxy-3-methylbutyric acid
transcription factor
colitis-associated cancer (CAC)
Lactobacillus paracasei BD5115
intestinal epithelial cells proliferation
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 2-hydroxy-3-methylbutyric acid
transcription factor
colitis-associated cancer (CAC)
Lactobacillus paracasei BD5115
intestinal epithelial cells proliferation
url https://www.frontiersin.org/articles/10.3389/fnut.2022.799053/full
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