Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1733-8) contains supplementary material, which is available to authorized users.
Highlights
Evidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals
The expression profiles over time of CHIT1 differs for all three conditions while the profiles of some other genes, such as GRB2 and MAPK14, show most difference in only one treatment compared to the control group (Ctrl)
Genes are represented as nodes in the networks, all these genes have time profiles that are significantly different in the treatment than in the control
Summary
Evidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals. Evidence is accumulating that perturbations of the early life colonization of the gastro-intestinal (GI) tract by microbes induce long-lasting health effects in individuals [1, 2]. Though these effects have been studied and documented, the system components involved in the. Life environmental factors, such as caesarean delivery [17], breastfeeding [18,19,20], exposure to stress [21, 22], and the use of antibiotics [23, 24] influence the microbial colonisation of the gut and affect the development and programming of the mucosal and systemic immune system [16, 25]. Such early life factors may result in variation of the abilities of the microbiota to ferment carbohydrates into short-chain fatty acids [26] and/or to ferment indigestible proteins in later stages of life
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