title: Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease.
abstract: OBJECTIVE
  We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months.
  
  
  METHODS
  This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to-relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline.
  
  
  RESULTS
  A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy.
  
  
  CONCLUSIONS
  BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation.
authors.affiliation: Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Juanola
authors.affiliation: Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sempere
authors.affiliation: Servicio Digestivo, Hospital Universitario de Elche, Alicante, Spain.
authors.forename: Marifé
authors.initials: M
authors.lastname: García
authors.affiliation: Hospital Clínico Universitario de San Juan, Alicante, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Laveda
authors.affiliation: Hospital Clínico Universitario de San Juan, Alicante, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zìrich, Zìrich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.affiliation: Department of Gastroenterology, University Clinic for Visceral Medicine, Inselspital, Bern, Switzerland.
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zìrich, Zìrich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.|Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan de Alicante, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
mesh_terms: D000328:Adult; D018988:Bacterial Translocation; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology*; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000032:analysis*; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D013030:Spain; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004269:DNA, Bacterial; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha