title: Microbial Factors Associated with Postoperative Crohn's Disease Recurrence.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Wright
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia mkamm@unimelb.edu.au.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kamm
authors.affiliation: Enteric Virus Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
authors.forename: Josef
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Centre for Systems Genomics, and Department of Pathology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Teo
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Peter De
authors.initials: P
authors.lastname: Cruz
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Hamilton
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ritchie
authors.affiliation: Centre for Systems Genomics, and Department of Pathology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.affiliation: Enteric Virus Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.|Department of Microbiology, La Trobe University, Melbourne, VIC, Australia.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Kirkwood
mesh_terms: D000328:Adult; D003082:Colectomy / Q000009:adverse effects / Q000379:methods; D003113:Colonoscopy / Q000379:methods; D003424:Crohn Disease / Q000382:microbiology / Q000473:pathology / Q000523:psychology / Q000601:surgery; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000382:microbiology / Q000523:psychology; D011511:Proteus / Q000302:isolation & purification; D012008:Recurrence; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000503:physiopathology; D013223:Statistics as Topic
keywords: Microbiota; Proteus; inflammatory bowel disease; microbiome