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

Nature communications 2020 Mar 12

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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.

Citation

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. Impact of the gut microbiota on the m6A epitranscriptome of mouse cecum and liver. Nature communications. 2020 Mar 12;11(1):1344