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

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 and Pascale Cossart ()
Additional contact information
Sabrina Jabs: Unité des Interactions Bactéries-Cellules, Institut Pasteur, U604 Institut National de la Santé et de la Recherche Médicale, USC 2020 Institut National de la Recherche Agronomique
Anne Biton: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Christophe Bécavin: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Marie-Anne Nahori: Unité des Interactions Bactéries-Cellules, Institut Pasteur, U604 Institut National de la Santé et de la Recherche Médicale, USC 2020 Institut National de la Recherche Agronomique
Amine Ghozlane: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Alessandro Pagliuso: Unité des Interactions Bactéries-Cellules, Institut Pasteur, U604 Institut National de la Santé et de la Recherche Médicale, USC 2020 Institut National de la Recherche Agronomique
Giulia Spanò: Unité des Interactions Bactéries-Cellules, Institut Pasteur, U604 Institut National de la Santé et de la Recherche Médicale, USC 2020 Institut National de la Recherche Agronomique
Vincent Guérineau: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay
David Touboul: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay
Quentin Giai Gianetto: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Thibault Chaze: Unité de spectrométrie de masse et Protéomique, CNRS USR 2000, Institut Pasteur
Mariette Matondo: Unité de spectrométrie de masse et Protéomique, CNRS USR 2000, Institut Pasteur
Marie-Agnès Dillies: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Pascale Cossart: Unité des Interactions Bactéries-Cellules, Institut Pasteur, U604 Institut National de la Santé et de la Recherche Médicale, USC 2020 Institut National de la Recherche Agronomique

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15126-x

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