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Int J Biol Sci 2012; 8(2):171-186. doi:10.7150/ijbs.8.171

Research Paper

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

Natasha Singh1, Elize A. Shirdel2,3, Levi Waldron2,#, Regan-Heng Zhang1,*, Igor Jurisica2,3,4, Elena M. Comelli1✉

1. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada
2. Ontario Cancer Institute, Princess Margaret Hospital, University Health Network and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada
3. Department of Medical Biophysics, University of Toronto, Ontario, Canada
4. Department of Computer Science, University of Toronto, Ontario, Canada
# Present address: Department of Biostatistics, Harvard School of Public Health, Building 1, Room 412C, 655 Huntington Avenue, Boston, Massachusetts 02115, USA
* Present address: The Biomedical Research Centre, Department of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada

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.

Keywords: gut microbiota, microRNA, caecum, intestinal barrier, glycosylation, mouse

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Singh N, Shirdel EA, Waldron L, Zhang RH, Jurisica I, Comelli EM. The Murine Caecal MicroRNA Signature Depends on the Presence of the Endogenous Microbiota. Int J Biol Sci 2012; 8(2):171-186. doi:10.7150/ijbs.8.171. Available from http://www.ijbs.com/v08p0171.htm