title: Microbiota modulate host gene expression via microRNAs.
abstract: Microbiota are known to modulate host gene expression, yet the underlying molecular mechanisms remain elusive. MicroRNAs (miRNAs) are importantly implicated in many cellular functions by post-transcriptionally regulating gene expression via binding to the 3'-untranslated regions (3'-UTRs) of the target mRNAs. However, a role for miRNAs in microbiota-host interactions remains unknown. Here we investigated if miRNAs are involved in microbiota-mediated regulation of host gene expression. Germ-free mice were colonized with the microbiota from pathogen-free mice. Comparative profiling of miRNA expression using miRNA arrays revealed one and eight miRNAs that were differently expressed in the ileum and the colon, respectively, of colonized mice relative to germ-free mice. A computational approach was then employed to predict genes that were potentially targeted by the dysregulated miRNAs during colonization. Overlapping the miRNA potential targets with the microbiota-induced dysregulated genes detected by a DNA microarray performed in parallel revealed several host genes that were regulated by miRNAs in response to colonization. Among them, Abcc3 was identified as a highly potential miRNA target during colonization. Using the murine macrophage RAW 264.7 cell line, we demonstrated that mmu-miR-665, which was dysregulated during colonization, down-regulated Abcc3 expression by directly targeting the Abcc3 3'-UTR. In conclusion, our study demonstrates that microbiota modulate host microRNA expression, which could in turn regulate host gene expression.
authors.affiliation: Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America. gdalmas@emory.edu
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dalmasso
authors.forename: Hang Thi Thu
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yan
authors.forename: Hamed
authors.initials: H
authors.lastname: Laroui
authors.forename: Moiz A
authors.initials: MA
authors.lastname: Charania
authors.forename: Saravanan
authors.initials: S
authors.lastname: Ayyadurai
authors.forename: Shanthi V
authors.initials: SV
authors.lastname: Sitaraman
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D020413:3' Untranslated Regions; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D035683:MicroRNAs; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C114462:multidrug resistance-associated protein 3