The Murine Caecal MicroRNA Signature Depends on the Presence of the Endogenous Microbiota

Abstract

The intestinal messenger RNA expression signature is affected by the presence and composition of the endogenous microbiota, with effects on host physiology. The intestine is also characterized by a distinctive micronome. However, it is not known if microbes also impact intestinal gene expression epigenetically. We investigated if the murine caecal microRNA expression signature depends on the presence of the microbiota, and the potential implications of this interaction on intestinal barrier function. Three hundred and thirty four microRNAs were detectable in the caecum of germ-free and conventional male mice and 16 were differentially expressed, with samples from the two groups clustering separately based on their expression patterns. Through a combination of computational and gene expression analyses, including the use of our curated list of 527 genes involved in intestinal barrier regulation, 2,755 putative targets of modulated microRNAs were identified, including 34 intestinal barrier-related genes encoding for junctional and mucus layer proteins and involved in immune regulation. This study shows that the endogenous microbiota influences the caecal microRNA expression signature, suggesting that microRNA modulation is another mechanism through which commensal bacteria impact the regulation of the barrier function and intestinal homeostasis. Through microRNAs, the gut microbiota may impinge a much larger number of genes than expected, particularly in diseases where its composition is altered. In this perspective, abnormally expressed microRNAs could be considered as novel therapeutic targets.

MicroRNAs: Decoders of Dysbiosis into Metabolic Diseases?

“…This latter property appears to be based on the capacity of miRs to enter bacteria and directly impact on microbial metabolism. In accordance with the aforementioned work, Singh and colleagues found that caecal miRs profile depends on the presence of the endogenous gut microbiota in mice [81].…”

Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development

“…The expression of 4.8% of all cecal miRNAs was reported to be differentially expressed when comparing GF and conventionally reared mice (Singh et al, 2012). The potential targets of the differentially expressed miRNAs included genes involved in regulating the intestinal barrier through encoding junctional and mucus layer proteins (Singh et al, 2012). Furthermore, the miRNAs differentially expressed in GF and conventional mice also targeted genes involved in regulating the expression of MHC Class I and II proteins (Singh et al, 2012).…”

“…An interplay between microRNA expression in GIT tissues and the microbiome has been suggested as one possible mechanism to regulate and integrate normal development and function of the mucosal immune system (Masotti, 2012). The expression of 4.8% of all cecal miRNAs was reported to be differentially expressed when comparing GF and conventionally reared mice (Singh et al, 2012). The potential targets of the differentially expressed miRNAs included genes involved in regulating the intestinal barrier through encoding junctional and mucus layer proteins (Singh et al, 2012).…”

“…The potential targets of the differentially expressed miRNAs included genes involved in regulating the intestinal barrier through encoding junctional and mucus layer proteins (Singh et al, 2012). Furthermore, the miRNAs differentially expressed in GF and conventional mice also targeted genes involved in regulating the expression of MHC Class I and II proteins (Singh et al, 2012). Therefore, the results of this study suggested that modulation of miRNAs by the gut microflora may play an important role in regulating the development of both the mucosal barrier and host immune responses in the GIT.…”

Commentary: Cross-talks between microbiota and microRNAs

“…Given their strength in numbers (~100 trillion) and wellestablished influence on host physiology -particularly by influencing intestinal epithelial cell gene expression -the potential for the gut microbiota to influence miRNA expression in the gut is intuitive. Indeed, recent investigations into this concept have suggested a role for the gut microbiota in eliciting miRNA expression changes throughout the gut [4][5][6][7][8]. A recent paper published in the mBio journal outlined the findings of a study into the miRNA expression response following oral Listeria monocytogenes infection between germfree and conventional mice [9], and deduced that there was differential expression likely mediated through the gut microbiota.…”