The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine

The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m6A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m6A modification of the host, it remains u...

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Main Authors: Zhuoyu Xiao, Sun Liu, Zengguang Li, Jinru Cui, Hailan Wang, Zihan Wang, Qihuan Ren, Laixin Xia, Zhijian Wang, Yuan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.882994/full
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author Zhuoyu Xiao
Sun Liu
Zengguang Li
Jinru Cui
Hailan Wang
Zihan Wang
Qihuan Ren
Laixin Xia
Zhijian Wang
Yuan Li
author_facet Zhuoyu Xiao
Sun Liu
Zengguang Li
Jinru Cui
Hailan Wang
Zihan Wang
Qihuan Ren
Laixin Xia
Zhijian Wang
Yuan Li
author_sort Zhuoyu Xiao
collection DOAJ
description The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m6A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m6A modification of the host, it remains unclear whether the maternal microbiome affects m6A epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of m6A writers and erasers, as well as the m6A methylome of the mouse fetal brain and intestine on embryonic day 18. From the m6A profiles, we identified 2,655 and 2,252 m6A modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these m6A-modified genes were enriched in the neuro/intestinal developmental pathways, such as the Wnt signaling pathway. Finally, we verified that antibiotic treatment mostly recapitulated changes in m6A, and we further showed that the loss of heterozygosity of Mettl3 rescued m6A levels and the expression changes of some developmental genes in the fetal intestine that resulted from antibiotic treatment. Collectively, our data revealed that the maternal microbiome programs the m6A epitranscriptome of the mouse fetal brain and intestine.
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institution Kabale University
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publisher Frontiers Media S.A.
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spelling doaj-art-855a808ef4684206bde40aaeacebd70a2025-02-06T15:01:05ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-07-011010.3389/fcell.2022.882994882994The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and IntestineZhuoyu Xiao0Sun Liu1Zengguang Li2Jinru Cui3Hailan Wang4Zihan Wang5Qihuan Ren6Laixin Xia7Zhijian Wang8Yuan Li9Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaThe microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m6A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m6A modification of the host, it remains unclear whether the maternal microbiome affects m6A epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of m6A writers and erasers, as well as the m6A methylome of the mouse fetal brain and intestine on embryonic day 18. From the m6A profiles, we identified 2,655 and 2,252 m6A modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these m6A-modified genes were enriched in the neuro/intestinal developmental pathways, such as the Wnt signaling pathway. Finally, we verified that antibiotic treatment mostly recapitulated changes in m6A, and we further showed that the loss of heterozygosity of Mettl3 rescued m6A levels and the expression changes of some developmental genes in the fetal intestine that resulted from antibiotic treatment. Collectively, our data revealed that the maternal microbiome programs the m6A epitranscriptome of the mouse fetal brain and intestine.https://www.frontiersin.org/articles/10.3389/fcell.2022.882994/fullmaternal microbiomem6Afetal developmentWnt signaling pathwayMETTL3
spellingShingle Zhuoyu Xiao
Sun Liu
Zengguang Li
Jinru Cui
Hailan Wang
Zihan Wang
Qihuan Ren
Laixin Xia
Zhijian Wang
Yuan Li
The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
Frontiers in Cell and Developmental Biology
maternal microbiome
m6A
fetal development
Wnt signaling pathway
METTL3
title The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
title_full The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
title_fullStr The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
title_full_unstemmed The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
title_short The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
title_sort maternal microbiome programs the m6a epitranscriptome of the mouse fetal brain and intestine
topic maternal microbiome
m6A
fetal development
Wnt signaling pathway
METTL3
url https://www.frontiersin.org/articles/10.3389/fcell.2022.882994/full
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