Abstract
Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastro-intestinal tract with the main subtypes Crohn’s disease (CD) and ulcerative colitis (UC). IBD is growing rapidly in incidence and prevalence throughout the world and is strongly associated with an imbalance of the gut microbiota, although the pathogenesis is unknown. There are multiple conventional treatments, but moderate to severe IBD is treated successfully with anti-tumor necrosis factor alpha (TNF-α) infliximab (IFX). Many have studied the fecal microbiota in relation to IFX treatment, but studies on the mucosal microbiota composition during IFX treatment are scarce. Additionally, there is a problem that up to half of the patients receiving IFX do not have a good long-term response. There are no methods available to predict the response to IFX, which would be crucial to save from both high costs and possible side-effects. Previously, predictive markers of IFX response have been mostly investigated from the fecal microbiota composition. Methods Here the aim was therefore to investigate the mucosal microbiota composition of the gut during IFX treatment and to determine whether the gut mucosal microbiota composition differed between responders and non-responders to IFX. This was investigated in an exceptional cohort including 72 IBD patients from whom biopsy samples from both small- and large intestine and fecal samples were collected before, during and after IFX treatment. The IFX response was determined clinically and by colonoscopy at week 12 after start of treatment. The microbiota composition was determined by MiSeq sequencing targeting the 16S conserved rRNA regions of DNA extracted from the biopsies using an optimized repeated bead-beating isolation method. Additionally, the already published fecal fungal and bacterial microbiota composition was also included to get further comparison between these. Results Interestingly, the preliminary results of the mucosal bacterial microbiota also show that there is a significant difference between the response groups (p < 0.05), similar to the fecal microbiota composition. Thus, the IFX response groups could be distinguished based on the fecal and mucosal microbiota composition. Conclusion These results could, together with previously published results, provide an urgently needed diagnostic tool for IFX response prediction.
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