Microbial Factors Associated with Postoperative Crohn's Disease Recurrence

J Crohns Colitis. 2017 Feb;11(2):191-203. doi: 10.1093/ecco-jcc/jjw136. Epub 2016 Jul 27.

Abstract

Background and aims: The intestinal microbiota is a key antigenic driver in Crohn's disease [CD]. We aimed to identify changes in the gut microbiome associated with, and predictive of, disease recurrence and remission.

Methods: A total of 141 mucosal biopsy samples from 34 CD patients were obtained at surgical resection and at colonoscopy 6 and/or 18 months postoperatively; 28 control samples were obtained: 12 from healthy patients [healthy controls] and 16 from hemicolectomy patients [surgical controls]. Bacterial 16S ribosomal profiling was performed using the Illumina MiSeq platform.

Results: CD was associated with reduced alpha diversity when compared with healthy controls but not surgical controls [p < 0.001 and p = 0.666, respectively]. Beta diversity [composition] differed significantly between CD and both healthy [p < 0.001] and surgical [p = 0.022] controls, but did not differ significantly between those with and without endoscopic recurrence. There were significant taxonomic differences between recurrence and remission. Patients experiencing recurrence demonstrated elevated Proteus genera [p = 0.008] and reduced Faecalibacterium [p< 0.001]. Active smoking was associated with elevated levels of Proteus [p = 0.013] postoperatively. Low abundance of Faecalibacterium [< 0.1%] and detectable Proteus in the postoperative ileal mucosa was associated with a higher risk of recurrence (odds ratio [OR] 14 [1.7-110], p = 0.013 and 13 [1.1-150], p = 0.039, respectively) when corrected for smoking. A model of recurrence comprising the presence of Proteus, abundance of Faecalibacterium, and smoking status showed moderate accuracy (area under the curve [AUC] 0.740, 95% confidence interval [CI] [0.69-0.79]).

Conclusions: CD is associated with a microbial signature distinct from health. Microbial factors and smoking independently influence postoperative CD recurrence. The genus Proteus may play a role in the development of CD.

Keywords: Microbiota; Proteus; inflammatory bowel disease; microbiome.

MeSH terms

  • Adult
  • Colectomy* / adverse effects
  • Colectomy* / methods
  • Colonoscopy / methods
  • Crohn Disease* / microbiology
  • Crohn Disease* / pathology
  • Crohn Disease* / psychology
  • Crohn Disease* / surgery
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Ileum* / microbiology
  • Ileum* / pathology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Postoperative Complications* / diagnosis
  • Postoperative Complications* / microbiology
  • Postoperative Complications* / psychology
  • Proteus / isolation & purification
  • Recurrence
  • Risk Factors
  • Smoking* / epidemiology
  • Smoking* / physiopathology
  • Statistics as Topic