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

作者：Xiao, Zhuoyu; Liu, Sun; Li, Zengguang; Cui, Jinru; Wang, Hailan; Wang, Zihan; Ren, Qihuan; Xia, Laixin^*; Wang, Zhijian^*; Li, Yuan^*

来源：Frontiers in Cell and Developmental Biology, 2022, 10: 882994.

DOI：10.3389/fcell.2022.882994

• maternal microbiome
• m(6)A
• fetal development
• Wnt signaling pathway
• METTL3

The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m(6)A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m(6)A modification of the host, it remains unclear whether the maternal microbiome affects m(6)A epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of m(6)A writers and erasers, as well as the m(6)A methylome of the mouse fetal brain and intestine on embryonic day 18. From the m(6)A profiles, we identified 2,655 and 2,252 m(6)A modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these m(6)A-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 m(6)A, and we further showed that the loss of heterozygosity of Mettl3 rescued m(6)A 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 m(6)A epitranscriptome of the mouse fetal brain and intestine.

• 单位
  南方医科大学; y