Characteristics of mucosa-associated gut microbiota during treatment in Crohn's disease

摘要

BACKGROUND The dysbiosis of the gut microbiome is evident in Crohn's disease(CD) compared with healthy controls(HC), although the alterations from active CD to remission after treatment are unclear.AIM To characterize the mucosa-associated gut microbiota in patients with CD before and after the induction therapy.METHODS The basic information was collected from the subjects and the CD activity index(CDAI) was calculated in patients. A 16S rRNA sequencing approach was applied to determine the structures of microbial communities in mucosal samples including the terminal ileal, ascending colon, descending colon and rectum. The composition and function of mucosa-associated gut microbiota were compared between samples from the same cohort of patients before and after treatment.Differential taxa were identified to calculate the microbial dysbiosis index(MDI)and the correlation between MDI and CDAI was analyzed using Pearson correlation test. Predictive functional profiling of microbial communities was obtained with PICRUSt.RESULTS There were no significant differences in microbial richness among the four anatomical sites in individuals. Compared to active disease, the alpha diversity of CD in remission was increased towards the level of HC compared to the active stage. The principal coordinate analysis revealed that samples of active CD were clearly separated from those in remission, which clustered close to HC. Sixty-five genera were identified as differentially abundant between active and quiescent CD, with a loss of Fusobacterium and a gain of potential beneficial bacteria including Lactobacillus, Akkermansia, Roseburia, Ruminococcus and Lachnospira after the induction of remission. The combination of these taxa into a MDI showed a positive correlation with clinical disease severity and a negative correlation with species richness. The increased capacity for the inferred pathways including Lipopolysaccharide biosynthesis and Lipopolysaccharide biosynthesis proteins in patients before treatment negatively correlated with the abundance of Roseburia,Ruminococcus and Lachnospira.CONCLUSION The dysbiosis of mucosa-associated microbiota was associated with the disease phenotype and may become a potential diagnostic tool for the recurrence of disease.