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Article Dans Une Revue Scientific Reports Année : 2020

Methyl-donor supplementation prevents intestinal colonization by Adherent-invasive E. coli in a mouse model of crohn's disease

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Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-invasive Escherichia coli (AIEC) are frequently observed in Crohn's disease (CD) patients. Aiec bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn's disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients.
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hal-02917129 , version 1 (18-08-2020)

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Elodie Gimier, Mélissa Chervy, Allison Agus, Adeline Sivignon, Elisabeth Billard, et al.. Methyl-donor supplementation prevents intestinal colonization by Adherent-invasive E. coli in a mouse model of crohn's disease. Scientific Reports, 2020, 10, pp.12922. ⟨10.1038/s41598-020-69472-3⟩. ⟨hal-02917129⟩
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