Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon

ABSTRACT: Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems. Keywords: Expression profiling by array Mice received a control diet, or a diet supplemented with 10% dietary fibers for 10 days. After an overnight fast colon was removed, epithelial cells were scraped off, and subjected to gene expression profiling.

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld

PROVIDER: E-GEOD-59494 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon.

Lange Katja K Hugenholtz Floor F Jonathan Melliana C MC Schols Henk A HA Kleerebezem Michiel M Smidt Hauke H Müller Michael M Hooiveld Guido J E J GJ

Molecular nutrition & food research 20150617 8

<h4>Scope</h4>The aim of our study was to investigate and compare the effects of five fibers on the mucosal transcriptome, together with alterations in the luminal microbiota composition and SCFA concentrations in the colon.<h4>Methods and results</h4>Mice were fed fibers that differed in carbohydrate composition or a control diet for 10 days. Colonic gene expression profiles and luminal microbiota composition were determined by microarray techniques, and integrated using multivariate statistics ...[more]

PMID: 25914036

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Project description:Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. Mice were fed a Westernized high fat control diet, or the same diet supplemented with 0.5 µmol heme/g diet. One group of control and one group of heme mice received a mixture of broad spectrum Antibiotics (Abx) (ampicilin, neomycin and metronidazole) in their drinking water. After 14 days of intervention, mice were killed and gene expression was profiled in colon.

Dataset Information

Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon

Publications

Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon.

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