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| Status |
Public on Aug 21, 2022 |
| Title |
Deleterious effects of high sucrose diet on intestinal homeostasis in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
37 samples divided in 4 diet groups : Control Diet (CD), High Sucrose Diet (HSD) during 8 weeks or 16 weeks and HSD+CD (HSD 8 weeks + CD 8 weeks) and subdivided in two groups DSS-treated and not (DSS+/DSS-) ; CD DSS- ; N = 5 ; biological replicates / CD DSS+ ; N = 4 ; biological replicates / HSD8 DSS- ; N = 5 ; biological replicates / HSD8 DSS+ ; N = 5 ; biological replicates / HSD16 DSS- ; N = 5 ; biological replicates / HSD16 DSS+ ; N = 4 ; biological replicates / HSD+CD DSS- ; N = 5 ; biological replicates / HSD+CD DSS+ ; N = 4 ; biological replicates.
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| Contributor(s) |
Arnone D, Hergalant S, Peyrin-Biroulet L |
| Citation(s) |
34869528 |
| Submission date |
May 28, 2020 |
| Last update date |
Aug 25, 2022 |
| Contact name |
Sebastien Hergalant |
| Organization name |
INSERM
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| Department |
Bioinformatics
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| Lab |
NGERE
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| Street address |
Faculté de Médecine. 9 avenue de la forêt de Haye
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| City |
Vandoeuvre-lès-Nancy |
| ZIP/Postal code |
54505 |
| Country |
France |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA635681 |
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