Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease.

Gutiérrez, Ana; Zapater, Pedro; Juanola, Oriol; Sempere, Laura; García, Marifé; Laveda, Raquel; Martínez, Antonio; Scharl, Michael; González-Navajas, José M; Such, José; Wiest, Reiner; Rogler, Gerhard; Francés, Rubén (2016). Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease. American journal of gastroenterology, 111(4), pp. 529-540. Nature 10.1038/ajg.2016.8

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OBJECTIVES

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.

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