Persistent Diarrhea in Patients With Crohn's Disease After Mucosal Healing is Associated With Lower Diversity of the Intestinal Microbiome and Increased Dysbiosis.

Abstract Background & Aims In patients with inflammatory bowel diseases (IBD), symptoms do not always associate with the severity of endoscopic inflammation and can persist after mucosal healing. We investigated whether symptoms in patients with successfully treated IBD are related to composition of the intestinal microbiome. Methods We analyzed 590 tissue biopsies from 215 patients with IBD and 48 healthy individuals (controls). We obtained mucosal biopsies from 2 colon sites (ascending and rectosigmoid) and from the terminal ileum along with clinical data. Bacterial DNA was extracted from the biopsies and the V4 region of 16s rRNA sequenced by Miseq and processed using the QIIME v1.9 pipeline. Results Mucosal biopsies from patients with Crohn's disease (CD) who achieved mucosal healing (Mayo scores of 0–1 or SES-CD scores of 0–5) had lower Chao1 diversity than biopsies from patients with ulcerative colitis (UC) or unclassified IBD (IBD-U), or controls. After endoscopic evidence of improvement in patients with UC or IBD-U, diversity of the tissue-associated microbiota did not differ significantly from that of controls. Colon biopsies from patients with CD had lower microbial diversity, before and after healing (segmental endoscopic severity-CD scores, 0–2), than colon biopsies from controls (P Conclusions In an analysis of biopsies from patients with IBD and controls, we found that despite endoscopic evidence of improvement or remission, alpha diversity of the tissue-associated intestinal microbiome remained lower in patients with CD than in controls. This observation, along with the reduced Chao1 diversity and greater dysbiosis in intestinal microbiota of patients with residual symptoms of IBD, indicates that microbiome composition could be associated with persistent diarrhea.