Impact of the gut microbiota on the m6A epitranscriptome of mouse cecum and liver.

Authors:
Sabrina Jabs, Anne Biton, Christophe Bécavin, Marie-Anne Nahori, Amine Ghozlane, Alessandro Pagliuso, Giulia Spanò, Vincent Guérineau, David Touboul, Quentin Giai Gianetto, Thibault Chaze, Mariette Matondo, Marie-Agnès Dillies, Pascale Cossart
Year of publication:
2020
Volume:
11
Issue:
1
Issn:
2041-1723
Journal title abbreviated:
NAT COMMUN
Journal title long:
Nature communications
Impact factor:
12.121
Abstract:
The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. Here we examine whether host epitranscriptomic marks are affected by the gut microbiota. We use methylated RNA-immunoprecipitation and sequencing (MeRIP-seq) to identify N6-methyladenosine (m6A) modifications in mRNA of mice carrying conventional, modified, or no microbiota. We find that variations in the gut microbiota correlate with m6A modifications in the cecum, and to a lesser extent in the liver, affecting pathways related to metabolism, inflammation and antimicrobial responses. We analyze expression levels of several known writer and eraser enzymes, and find that the methyltransferase Mettl16 is downregulated in absence of a microbiota, and one of its target mRNAs, encoding S-adenosylmethionine synthase Mat2a, is less methylated. We furthermore show that Akkermansia muciniphila and Lactobacillus plantarum affect specific m6A modifications in mono-associated mice. Our results highlight epitranscriptomic modifications as an additional level of interaction between commensal bacteria and their host.