Effects Of Exclusive Enteral Nutrition In Treatment Of Active Crohn’s Disease In Adults And Its Effects On The Gut Microbiota

Part 1Retrospective Study:Exclusive Enteral Nutrition in the treatment of adult refractory Crohn’s DiseaseBackground:Crohn’s Disease(CD)is a chronic inflammatory bowel disease of unknown etiology.Despite the increasing incidence of CD,its treatment remains unsatisfying.There is growing evidence demonstrating that Exclusive Enteral Nutrition(EEN)has therapeutic value in CD to certain extend.Though EEN is considered a first-line treatment for children with CD,its use in adults is controversial.Objective:To study the clinical efficacy of EEN on patients with refractory CD through evaluating variations in inflammation markers,disease activity and nutritional status before and after thetreatment,and thus investigating factors that have effects on the efficacy of EEN.Methods:We collected and retrospectively analyzed the clinical data of 25 refractory CD patients that met the inclusion criteria and received EEN from Oct.2015 to Jun.2019 in Zhongshan Hospital affiliated to Xiamen University,including patients’ WBC,NEUT%,HGB,PLT,TP,ALB,CRP,PCT,ESR,CDAI,BMI before the treatment and 1 week,2 weeks,3 weeks,4 weeks,6 weeks,8 weeks after.The software IBM SPSS 24.0 was used for statistical analysis.Results:The TP,ALB,HGB level of 25 patients increased after 8 weeks of EEN treatment,where WBC,NEUT%,PLT,ESR decreased.There is a statistically significant difference 2 weeks after the treatment(P<0.05)for WBC and NEUT%,3 weeks after(P<0.05)for ALB and ESR,and 4 weeks after(P<0.05)for HBG and PLT.Meanwhile,TP decreased drastically after 1 week of treatment but steadily improved benefiting from EEN,and eventually demonstrated a statistically significant difference 8 weeks later(P<0.05).On the other hand,there is a substantial rise in BMI with a decrease in CDAI 8 weeks after the treatment(P<0.05).To further study the effect of combinational therapy on the efficacy of EEN,the treatment group was divided into exclusive EEN group and combinational medicine EEN group.The intra-group analysis revealed that there was no significant statistical difference in laboratory indicators after 8 weeks of EEN treatment(P>0.05).Conclusions:EEN can improve the nutritional status of CD patients and reduce disease activity,and is effective on adult refractory CD.The effect of combinational therapy on the efficacy of ENN is indistinct,and the effect of lesion and course of treatment on it still needs to be further examined.Part 2Effects of Exclusive Enteral Nutrition on the gut microbiota in adultCrohn’s diseaseBackground:The pathogenesis of Crohn’s Disease(CD)is complex and thought to be related to environmental,immune,genetic,microbial and other factors.If the balance between host and gut microbes in CD patients is broken,it may trigger an immune-inflammatory response in susceptible populations.The clinical application of Exclusive Enteral Nutrition(EEN)in CD has attracted more and more attention,but the exact mechanism still remains unexplored.Assessing changes in the intestinal microbiota during EEN may offer clues to the etiology and treatment of CD.Objective:To study the gut microbiota differences between adult CD patients and normal healthy people,and to compare the changes of intestinal flora in CD patients before and after EEN,we investigated the relationship between the gut microbiota and CD pathogenesis,and the mechanism how EEN induces a remission on CD.Methods:Fecal samples of 5 confirmed adult CD patients and 10 healthy people were collected,together with those of 5 CD patients after 2 and 6 weeks treatment of EEN.Then 16SrDNA sequencing was used to analyze the composition and function of the gut microbiota.Results:Through 16SrDNA sequencing,it was found that the gut microbiota of CD patients was significantly less diverse than that of a healthy control group,and the species composition was also significantly different.After EEN treatment,it was found that the nutritional status and inflammatory degree of CD patients could be effectively improved,which is especially true for WBC,NEUT%,PLT,and CDAI that decreased with statistically significant differences(P<0.05).After analyzing the gut microbiota of CD patients before and after 2 or 6 weeks treatment of EEN,we found that the gut microbiota diversity of CD patients during EEN further decreased,and species abundance changed significantly.At both phyla and genus levels,the number of bacteria with pro-inflammatory properties([Ruminococcus]_gnavus_group,Escherichia-Shigella,Veillonella,Rothia,Streptococcus,etc.)decreased,while the number of bacteria with anti-inflammatory properties(Alistipes,etc.)increased or decreased.Conclusion:Compared with healthy people,CD patients showed significant differences in gut microbiota diversity and species composition.EEN can effectively induce remission in adult CD,its mechanism may be mediated by the destruction of established microbiota associated with CD,thereby recolonizing and establishing a more balanced community of interactions with the host.