Abstract
BackgroundHigh-protein diets (HPD) alter the large intestine microbiota composition in association with a metabolic shift towards protein degradation. Some amino acid-derived metabolites produced by the colon bacteria are beneficial for the mucosa while others are deleterious at high concentrations. The aim of the present work was to define the colonic epithelial response to an HPD. Transcriptome profiling was performed on colonocytes of rats fed an HPD or an isocaloric normal-protein diet (NPD) for 2 weeks.ResultsThe HPD downregulated the expression of genes notably implicated in pathways related to cellular metabolism, NF-κB signaling, DNA repair, glutathione metabolism and cellular adhesion in colonocytes. In contrast, the HPD upregulated the expression of genes related to cell proliferation and chemical barrier function. These changes at the mRNA level in colonocytes were not associated with detrimental effects of the HPD on DNA integrity (comet assay), epithelium renewal (quantification of proliferation and apoptosis markers by immunohistochemistry and western blot) and colonic barrier integrity (Ussing chamber experiments).ConclusionThe modifications of the luminal environment after an HPD were associated with maintenance of the colonic homeostasis that might be the result of adaptive processes in the epithelium related to the observed transcriptional regulations.
Highlights
High-protein diets (HPD) alter the large intestine microbiota composition in association with a metabolic shift towards protein degradation
It was concluded from microarray experiments that an HPD upregulates in rat colonic mucosa the expression of genes implicated in glutathione metabolism, chemotaxis, tumor necrosis factor-α signaling and apoptosis while it downregulates genes related to oxidative phosphorylation, glycosylation of mucins and innate immune responses [8]
Since the colonic mucosa contains a cell mixture from epithelium, lamina propia and muscularis mucosae layers, it is not possible to determine from that study what are the effects of HPD on colonic epithelial cells that are directly exposed to luminal changes induced by these diets
Summary
High-protein diets (HPD) alter the large intestine microbiota composition in association with a metabolic shift towards protein degradation. Modifications of the luminal environment are known to affect the colonic epithelium and may result in colonic homeostasis perturbation by alteration of the barrier function, modification of the epithelial renewal and impairment of the mucosal immune response [1]. In HPD-fed piglets, mucin gene expression as well as pro- and anti-inflammatory cytokines are upregulated in the colonic mucosa without modification of the histological aspect [18, 19]. In this latter animal model, there is no change in colonic barrier function after the HPD [20]. Since the colonic mucosa contains a cell mixture from epithelium, lamina propia and muscularis mucosae layers, it is not possible to determine from that study what are the effects of HPD on colonic epithelial cells that are directly exposed to luminal changes induced by these diets
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