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

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 (m 6 A) modifications in mRNA of mice carrying conventional, modified, or no microbiota. We find that variations in the gut microbiota correlate with m 6 A 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 m 6 A modifications in mono-associated mice. Our results highlight epitranscriptomic modifications as an additional level of interaction between commensal bacteria and their host.

A New Model of Spontaneous Colitis in Mice Induced by Deletion of an RNA m6A Methyltransferase Component METTL14 in T Cells

“…Similar results have been shown at the organ level in which the microbiome has been reported to affect m 6 A level in brain, intestine, and liver. 29 The most significantly affected pathway is the NOTCH signaling pathway, which has been shown to regulate T cell homeostasis and differentiation. 30 It is not clear whether the dysbiosis leads to the inflammation or is a secondary phenomenon.…”

Proposed Neuroimmune Roles of Dimethyl Fumarate, Bupropion, S-Adenosylmethionine, and Vitamin D3 in Affording a Chronically Ill Patient Sustained Relief from Inflammation and Major Depression

“…Epigenetic reactions are reversible chromatin (gene and protein) alterations that occur in two forms, methylation and acetylations. With methylation, gene and chromatin structures are not available for transcription by replication enzymes; however, with acetylation of lysine or arginine residues in chromatin (histones), gene sequences are available to replication enzymes and transcription may occur [ 100 , 101 , 102 , 103 , 104 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. To help understand and these reactions, as well as epigenetic protocols, the reader is advised to consult the text edited by Tollefsbol [ 111 ].…”

Pathogenic Biohacking: Induction, Modulation and Subversion of Host Transcriptional Responses by Listeria monocytogenes

“…Another level of complexity is introduced when the presence of other bacterial species, such as the components of the microbiota, are considered. Recent advances in microbiome research have shown that the gut microbiota can influence intestinal homeostasis and immunity by modulating host epitranscriptomic [133] and epigenetic modifications [134][135][136]. Lm is known to produce bacteriocins that kill other bacteria to promote its own infection, therefore, it may also be able to affect the transcriptional profile of its host by targeting specific members of the host gut microbiome [137,138].…”