Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Maternal exposure to a Western-style diet causes differences in microbiota composition and gene expression in the intestine of suckling mouse pups

ABSTRACT: During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring. Small intestine and colon were isolated from two-week-old pups of dams fed a low- or Western-style high fat/cholesterol diet and subjected to gene expression profiling.

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld

PROVIDER: E-GEOD-72705 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Maternal exposure to a Western-style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups.

Steegenga Wilma T WT Mischke Mona M Lute Carolien C Boekschoten Mark V MV Lendvai Agnes A Pruis Maurien G M MG Verkade Henkjan J HJ van de Heijning Bert J M BJ Boekhorst Jos J Timmerman Harro M HM Plösch Torsten T Müller Michael M Hooiveld Guido J E J GJ

Molecular nutrition & food research 20160712 1

<h4>Scope</h4>The long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident. The effects of maternal nutrition on the developing intestine are still underexplored.<h4>Methods and results</h4>In this study, we observed (1) altered microbiota composition of the colonic luminal content, and (2) differential gene expression in the intestinal wall in 2-week-old mouse pups born from dams exposed to a Western-style (WS) diet during the perinata ...[more]

PMID: 27129739

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Project description:There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnlγ). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes. Small intestine and colon were isolated from two-week old pups of dams fed a low-fat diet and subjected to gene expression profiling

Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.

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Dataset Information

Maternal exposure to a Western-style diet causes differences in microbiota composition and gene expression in the intestine of suckling mouse pups

Publications

Maternal exposure to a Western-style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups.

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