Bacterial DNA a potential biomarker of Crohn's relapse

Last Updated: 2016-03-17

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - In patients with Crohn's disease in remission, bacterial DNA (bactDNA) translocation may be a biomarker that can identify who is more likely to flare, according to new research.

Bacterial DNA translocation into blood is an independent risk factor for relapse at six months and is also independently associated with an increased risk of hospitalization, treatment change, and steroids initiation, the study authors, led by Dr. Ana Gutierrez of Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Spain, reported online February 23 in the American Journal of Gastroenterology.

Dr. Gutierrez and colleagues conducted a prospective, multicenter study of Crohn's disease patients with a Crohn's disease activity index (CDAI) under 150. The primary endpoint was time-to-relapse, with CDAI over 150 in the following six months.

At baseline, the authors determined BactDNA fragments in blood, the nucleotide-binding oligomerization domain containing NOD2 genotype, and serum cytokine levels.

Of the 288 patients included in their study, they identified BactDNA in 98 patients (34.0%) and found a variant-NOD2 genotype in 114 patients (39.6%). Overall, 40 patients (14%) relapsed during follow-up.

On multivariate survival analysis, bactDNA was an independent risk factor of flare (hazard ratio 8.75).

At six months, logistic regression analysis showed bactDNA to be a significant independent predictor of hospitalization (odds ratio 11.9, p<0.001), starting steroids (OR 8.5, p<0.001), and treatment change (OR 3.5, p=0.002).

The authors found no relationship between bactDNA and mucosal lesions in patients with colonoscopy at admission.

In patients with bactDNA or a variant-NOD2 genotype, serum pro-inflammatory cytokines increased significantly.

The combination of both factors led to decreased anti-tumor necrosis factor-alpha levels and a higher percentage of patients on intensified anti-TNF therapy.

"Gut bacterial translocation is a common phenomenon known to occur in Crohn's disease, the true 'leaky gut' disease. With improved methods now able to detect bactDNA fragments within the picogram level in blood, the investigators were able to demonstrate that as many as 34% of asymptomatic Crohn's disease patients had bactDNA in their blood samples," Dr. Caroline Hwang, associate medical director of the Center for Inflammatory Bowel Disease at Keck Medicine of the University of Southern California in Los Angeles, told Reuters Health by email.

"More importantly, bactDNA was predictive of patients relapsing, requiring hospitalization, surgery, or escalation of therapy to anti-TNF drugs or steroids," said Dr. Hwang, who was not involved in the research. "The authors make a good case that bactDNA could be a promising biomarker to identify patients who might be more likely to flare -- potentially even more sensitive than colonoscopy (our gold standard)," she said.

Dr. James F. Marion, professor of medicine and gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, told Reuters Health by email, "The findings are intriguing. This study gives us an early and important clue that a patient is at risk for a flare-up of disease so that we may intervene before the damage occurs."

"Too often, patients with inflammation from Crohn's disease present too long after inflammation has already caused damage, and therapy is less effective," he added. "We are always on the lookout for clues that predict whether a patient is likely to become ill before they manifest obvious symptoms. The earlier we intervene the more effective treatments can be."

Dr. Fernando Velayos, associate professor of medicine and associate director of translational research at the Center for Crohn's and Colitis at the University of California, San Francisco, told Reuters Health by email, "The study does not elucidate whether the bacterial fragments are causal for a future flare (less likely) or are a simple product of an impaired lining of the intestine (more likely), but it does create an interesting line of investigation as to whether we can use this observation to predict future relapse in the clinic."

"The identification of a blood test that can change based on the health of the gut (presumably the healthy gut does not allow significant translocation whereas an unhealthy one does) is quite exciting," Dr. Velayos said. "I do not think that this was the original intent of the study, but I think that if this can be developed further it can be a powerful clinical tool that can be measured over time and identify those who may relapse, months before they do."

The corresponding author did not respond to requests for comment.

AbbVie and the European Regional Development Fund co-funded the study. The authors and Drs. Marion, Velayos and Hwang declared no conflicts of interest with the study.

SOURCE: http://bit.ly/1UDDTfj

Am J Gastroenterol 2016.