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Genome Biol. 2015 Mar 28;16:62. doi: 10.1186/s13059-015-0614-4.

Site-specific programming of the host epithelial transcriptome by the gut microbiota.

Author information

1
The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, 41345, Sweden. Felix.Sommer@wlab.gu.se.
2
Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, 41296, Sweden. intawat@chalmers.se.
3
Present Address: Comparative Genomics Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37831, USA. intawat@chalmers.se.
4
The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, 41345, Sweden. Nina.Sommer@wlab.gu.se.
5
The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, 41345, Sweden. Per.Fogelstrand@wlab.gu.se.
6
The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, 41345, Sweden. fredrik.backhed@wlab.gu.se.
7
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark. fredrik.backhed@wlab.gu.se.

Abstract

BACKGROUND:

The intestinal epithelium separates us from the microbiota but also interacts with it and thus affects host immune status and physiology. Previous studies investigated microbiota-induced responses in the gut using intact tissues or unfractionated epithelial cells, thereby limiting conclusions about regional differences in the epithelium. Here, we sought to investigate microbiota-induced transcriptional responses in specific fractions of intestinal epithelial cells. To this end, we used microarray analysis of laser capture microdissection (LCM)-harvested ileal and colonic tip and crypt epithelial fractions from germ-free and conventionally raised mice and from mice during the time course of colonization.

RESULTS:

We found that about 10% of the host's transcriptome was microbially regulated, mainly including genes annotated with functions in immunity, cell proliferation, and metabolism. The microbial impact on host gene expression was highly site specific, as epithelial responses to the microbiota differed between cell fractions. Specific transcriptional regulators were enriched in each fraction. In general, the gut microbiota induced a more rapid response in the colon than in the ileum.

CONCLUSIONS:

Our study indicates that the microbiota engage different regulatory networks to alter host gene expression in a particular niche. Understanding host-microbiota interactions on a cellular level may facilitate signaling pathways that contribute to health and disease and thus provide new therapeutic strategies.

PMID:
25887251
PMCID:
PMC4404278
DOI:
10.1186/s13059-015-0614-4
[Indexed for MEDLINE]
Free PMC Article

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