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Deleterious effects of high sucrose diet on intestinal homeostasis in mice

ABSTRACT: Objective Western Diet (WD) appears to be an important factor associated with inflammatory bowel diseases (IBD). Refined sugars represent up to 40% of caloric intake in industrialized countries. Unlike fats, the impact of dietary sugar on healthy and inflamed intestine remains poorly described. Design We investigated the effects of a high sucrose diet (HSD) on dextran sulfate sodium (DSS)-induced colitis and on healthy intestine in mice. Several techniques ranging from macroscopic to molecular were used in vivo and direct effect of sugars was examined in cellulo on Caco-2 cell distinguishing differential effect of fructose and glucose. Results During established colitis in mice, HSD aggravated inflammation by increasing gut permeability, raising immune cells in spleen and impairing autophagy process in colonic mucosa. On healthy intestine, HSD caused spontaneous endoscopic lesions, systemic broad immunosuppression and dysregulation of stress-related genes, associated with gut microbiota dysbiosis. Global reprogramming of colonic transcriptome was detected in HSD-fed mice and amazingly, functional annotations demonstrated association with IBD and “colitis” without DSS-treatment. In vitro, low dose of fructose as well as high dose of glucose induced alteration of junctions confirming the deleterious effects of sugar on intestine. These effects seem to be partially reversible on microbiome and transcriptome of mice after switching back to normal diet. Conclusions Our results demonstrated for the first time that under pathological conditions mimicking pre-diabetes (mild hyperglycemia-associated with overweight), a pre-IBD state is established and depending on host sensitivity, in colitis conditions, this exacerbates the inflammation severity by disturbing cell-cell junction organization and autophagy process.

ORGANISM(S): Mus musculus

PROVIDER: GSE151400 | GEO | 2022/08/21

REPOSITORIES: GEO

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Project description:Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functional role of miRNAs in murine models of colitis facilitates elucidating the role of specific miRNAs in human IBD. The aim of this study was to determine the miRNA signature of murine models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miRNAs expression was accessed by microarray for acute and chronic murine model of colitis induced by DSS or TNBS. miR-21-deficient mouse and littermates controls were assessed in the standard DSS, TNBS and CD4+ T cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative RT-PCR. Th1 polarization was accessed by flow-cytometry and ELISA. Results: Alterations of in miRNAs expression were identified for acute and chronic DSS colitis and TNBS colitis, receptively. The Expression of miRs-21, -142-3p and -223 was were distinct between DSS and TNBS models while overlap of numerous miRNAs was seen. Importantly, miRs-19b, -192 and -215, that are decreased in IBD, were significantly decreased in all 4 models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis but not the DSS colitis models. Further assessment of the miR-21-deficient 1-/- mice revealed that the deletion of miR-21 results in the exacerbation of both the TNBS and T cell-transfer models of colitis. Conclusions: miRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T cell-mediated models of colitis provides further evidence that miRNAs play significant roles in the pathogenesis of IBD. miRNAs expression was accesed for acute and chronic murine model of colitis induced by DSS or TNBS.Total of 20 samples with duplicates were analyed in this study.

Project description:Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functional role of miRNAs in murine models of colitis facilitates elucidating the role of specific miRNAs in human IBD. The aim of this study was to determine the miRNA signature of murine models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miRNAs expression was accessed by microarray for acute and chronic murine model of colitis induced by DSS or TNBS. miR-21-deficient mouse and littermates controls were assessed in the standard DSS, TNBS and CD4+ T cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative RT-PCR. Th1 polarization was accessed by flow-cytometry and ELISA. Results: Alterations of in miRNAs expression were identified for acute and chronic DSS colitis and TNBS colitis, receptively. The Expression of miRs-21, -142-3p and -223 was were distinct between DSS and TNBS models while overlap of numerous miRNAs was seen. Importantly, miRs-19b, -192 and -215, that are decreased in IBD, were significantly decreased in all 4 models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis but not the DSS colitis models. Further assessment of the miR-21-deficient 1-/- mice revealed that the deletion of miR-21 results in the exacerbation of both the TNBS and T cell-transfer models of colitis. Conclusions: miRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T cell-mediated models of colitis provides further evidence that miRNAs play significant roles in the pathogenesis of IBD. Gene expression profiles were established for normal miR-21-/- mice and wild type c57BL/6 mice (WT). Total of 6 samples with replicates were included in this study.

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Deleterious effects of high sucrose diet on intestinal homeostasis in mice

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