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BMC Genomics

, 16:556

Non-human and non-rodent vertebrate genomics


BackgroundEvidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals. Understanding the mechanisms behind these effects will facilitate modulation of intestinal health. The objective of this study was to identify biological processes involved in these long lasting effects and the molecular factors that regulate them. We used an antibiotic and the same antibiotic in combination with stress on piglets as an early life perturbation. Then we used host gene expression data from the gut jejunum tissue and community-scale analysis of gut microbiota from the same location of the gut, at three different time-points to gauge the reaction to the perturbation. We analysed the data by a new combination of existing tools. First, we analysed the data in two dimensions, treatment and time, with quadratic regression analysis. Then we applied network-based data integration approaches to find correlations between host gene expression and the resident microbial species.

ResultsThe use of a new combination of data analysis tools allowed us to identify significant long-lasting differences in jejunal gene expression patterns resulting from the early life perturbations. In addition, we were able to identify potential key gene regulators hubs for these long-lasting effects. Furthermore, data integration also showed that there are a handful of bacterial groups that were associated with temporal changes in gene expression.

ConclusionThe applied systems-biology approach allowed us to take the first steps in unravelling biological processes involved in long lasting effects in the gut due to early life perturbations. The observed data are consistent with the hypothesis that these long lasting effects are due to differences in the programming of the gut immune system as induced by the temporary early life changes in the composition and-or diversity of microbiota in the gut.

KeywordsGene expression Microbiota Data-integration Long-term effects Early life perturbations Antibiotic Stress Pig intestine AbbreviationsGIGastrointestinal

Tr1Treatment group 1

Tr2Treatment group 2

CtrlControl group

DECDier experimenten commissie

PITChipPig intestinal tract chip

GEOGene Expression Omnibus

LIMMALInear models for microarray data

maSigProMicroarray significant profiles

GOGene ontology

FIFunctional interactions

MySQLMy structured query language

ANOVAAnalysis of variance

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1733-8 contains supplementary material, which is available to authorized users.

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Autor: Nirupama Benis - Dirkjan Schokker - Maria Suarez-Diez - Vitor AP Martins dos Santos - Hauke Smidt - Mari A Smits


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