| Crohn's disease is a chronic relapsing inflammatory intestinal disorder which can affect any part of the gastrointestinal tract——most commonly the terminal ileum.The incidence and prevalence of Crohn's disease is relatively high in North America and Europe,and it appears to be rising rapidly in Asia,especially in China,Japan and South Korea.Although the precise pathogenesis of Crohn's disease is unclear,it is believed that gene-environment interactions play a major role in Crohn's disease.miRNAs which could mediate environment-gene interactions are pivotal in regulating intestinal barrier function and intestinal immune response,and patients with Crohn's disease have unique miRNAs expression profiles in intestinal mucosa as well as serum.Diet is one of the environmental factors closely relevant to Crohn's disease,and exclusive enteral nutrition is an effective therapy for inducing remission.However,its mechanism remains inexact,which restricts the optimization of the exclusive enteral nutrition treatment regimens.New evidences are emerging that that dietary components can interact with genome and modify certain types of gene expression under a normal and variable genetic status through miRNAs,which may become either risk or protective factors for certain diseases.Therefore,our work was focused on the influence of exclusive enteral nutrition on the mucosal miRNAs expressions in Crohn's disease.At first,we investigated the miRNAs expression profile of both inflamed and non-inflamed terminal ileal mucosa of adult patients with active Crohn's disease.Sixteen Crohn's disease patients and 10 healthy adults were included in this study.miRNAs expression profile was measured using microarray technology,and then confirmed by using qRT-PCR.Our results indicated that aberrant expressions of miRNAs were not confined to inflamed,but preexisted in non-inflamed terminal ileal mucosa of adult patients with active Crohn's disease,and miRNAs profiles of inflamed and non-inflamed mucosa could distinguish them from each other.Validation by qRT-PCR confirmed that,comparing with healthy controls,expression of hsa-miR-192-5p was decreased in inflamed mucosa,and hsa-let-7b-5p,hsa-miR-495-5p were differentially expressed in non-inflamed mucosa.The expression of hsa-miR-361-3p was higher while hsa-miR-124-3p was lower in inflamed mucosa compared with non-inflamed one.Then,we investigated the efficacy of exclusive enteral nutrition therapy on inducing remission in adult patients with Crohn's disease.Firstly,we observed the effect of exclusive enteral nutrition on the quality of life in adult patients with Crohn's disease.We treated 13 patients with a polymeric enteral feed which was taken orally in the daytime and via a self-intubated nasogastric tube in the night for a period of 4 weeks.The results showed that 11 of 13 patients(84.6%)achieved clinical remission after treatment,and they had a significantly improvement in Inflammatory Bowel Disease Questionnaire score(P<0.001).Besides,8 patients(61.5%)expressed their willingness to receive this 4-week exclusive enteral nutrition treatment again to induce remission.Secondly,we tried to find out the effect of exclusive enteral nutrition on mucosal healing in adult patients with Crohn's disease.12 patients were treated with a 4-week exclusive enteral nutrition therapy described above,after exclusive enteral nutrition therapy,10(83.3%)patients achieved clinical remission.The rate of mucosal healing and rate of mucosal improvement was 41.7%&66.7%in the terminal ileum,and 25%&37.5%in the colon.The scores of terminal ileum was decreased significantly after exclusive enteral nutrition therapy,while scores of the colon had no meaningful changes.At last,we compared the miRNAs expression profiles of mucosa after exclusive enteral nutrition treatment with both mucosa in active Crohn's disease and healthy controls.Mucosa after exclusive enteral nutrition was collected from the area where lesions were present before therapy.Samples of 10 patients who achieved remission and underwent a secondary ileocolonoscopy,and 10 healthy controls were included in this study.miRNAs expression profile was firstly assessed by microarray technology and then verified by qRT-PCR.The results indicated that in patients who achieved remission after exclusive enteral nutrition therapy,the mucosal miRNAs expression profile was significantly altered,and it was more similar to the healthy control compared with the profile of non-inflamed mucosa before treatment.hsa-let-7b-5p was down-regulated in both inflamed and non-inflamed mucosa of active CD,but after EEN treatment,this differential expression was disappeared.hsa-miR-495-5p was up-regulated in all CD mucosa especially in inflamed mucosa before therapy,while hsa-miR-192-5p was down-regulated only in inflamed mucosa.Besides,the expressions of mucosal hsa-let-7b-5p was correlated with serum C-reactive protein levels both before and after exclusive enteral nutrition treatment.In conclusion,our study showed that exclusive enteral nutrition therapy were effective in inducing remission,improving patients' quality of life,and enhancing mucosal healing in adult patients with Crohn's disease.This effect of exclusive enteral nutrition induction therapy was associated with the modification of mucosal miRNAs expressions. |
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