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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Frontiers Media S.A.
2022-07-01
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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 |
issn | 2296-634X |
language | English |
publishDate | 2022-07-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cell and Developmental Biology |
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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