TY - JOUR

T1 - Site-specific programming of the host epithelial transcriptome by the gut microbiota

AU - Sommer, Felix

AU - Nookaew, Intawat

AU - Sommer, Nina

AU - Fogelstrand, Per

AU - Bäckhed, Gert Fredrik

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Animals

KW - Epithelial Cells

KW - Gastrointestinal Microbiome

KW - Gastrointestinal Tract

KW - Gene Expression Regulation

KW - Immune System

KW - Mice

KW - Microarray Analysis

KW - Microbiota

KW - Signal Transduction

KW - Transcriptome

U2 - 10.1186/s13059-015-0614-4

DO - 10.1186/s13059-015-0614-4

M3 - Journal article

C2 - 25887251

VL - 16

SP - 1

EP - 15

JO - Genome Biology (Online Edition)

JF - Genome Biology (Online Edition)

SN - 1474-7596

M1 - 62

ER -