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

Abstract

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.

Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice

“…m 6 A-dependent demethylation by FTO is associated with dopaminergic neurotransmission, adult neurogenesis, and axonal elongation. Moreover, elevated FTO levels crucially influence glucose and lipid metabolism-related gene expression in patients with DM [28]. In the present study, the FTO expression was reduced in the hippocampus of DCI mice, consistent with previous findings [29].…”

A Murine Model of Maternal Micronutrient Deficiencies and Gut Inflammatory Host-microbe Interactions in the Offspring

“…The timeline of the newly developed model (ie, late gestation through weaning) was rationally adapted to remain appropriate for studying the host-microbe interactions at intestinal mucosa. 19 , 20 , 21 Phenotypically, LM pups were characterized by reduced body hair with unnoticeable differences in weight ( Figure 1 B ) and tail length ( Figure 1 C ; as marker of stunting) compared with control (CON) pups. Although the role of malnourishment in reducing fertility rate or fecundity in mothers remains to be established, 22 the specific role of maternal multiple MNDs on offspring health outcomes has not been explored either.…”

N6‐ Methyladenosine defines a new checkpoint in γδ T cell development

“…[ 97 ] And other studies also demonstrate that Sox13 has highly enriched and specific m 6 A peaks in fetal intestine. [ 98 ] Taken together, different γδ T cell‐specific transcription factors may be regulated by different m 6 A binding proteins in the γδ T cell precursors during the γδ T cell lineage commitment.…”