Unknown,Transcriptomics,Genomics,Proteomics

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Identification of the core gene-regulatory network that governs the dynamic adaptation of intestinal homeostasis during conventionalization in mice


ABSTRACT: Molecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases. Expression profiling of jejunum, ileum, and colon tissue from germ-free and colonized mice at day 1,2,4,8,16 and 30.

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld 

PROVIDER: E-GEOD-32513 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation.

El Aidy Sahar S   Merrifield Claire A CA   Derrien Muriel M   van Baarlen Peter P   Hooiveld Guido G   Levenez Florence F   Doré Joel J   Dekker Jan J   Holmes Elaine E   Claus Sandrine P SP   Reijngoud Dirk-Jan DJ   Kleerebezem Michiel M  

Gut 20120621 9


<h4>Objective</h4>Proper interactions between the intestinal mucosa, gut microbiota and nutrient flow are required to establish homoeostasis of the host. Since the proximal part of the small intestine is the first region where these interactions occur, and since most of the nutrient absorption occurs in the jejunum, it is important to understand the dynamics of metabolic responses of the mucosa in this intestinal region.<h4>Design</h4>Germ-free mice aged 8-10 weeks were conventionalised with fae  ...[more]

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