While the causes of Crohn's disease are not well understood, recent research indicates an important role for an abnormal immune response to the microbes that live in the gut. In the largest study of its kind, researchers have now identified specific bacteria that are abnormally increased or decreased when Crohn's disease develops. The findings, which appear in the Cell Press journal Cell Host & Microbe, suggest which microbial metabolites could be targeted to treat patients with this chronic and currently incurable inflammatory bowel disease.
Twenty-eight gastroenterology centers across North America have been working together to uncover how microbes contribute to the inflammatory cascade of Crohn's disease. Researchers took biopsies from 447 individuals with new-onset Crohn's disease and 221 nonaffected individuals at multiple locations along the gastrointestinal tract and then looked for differences between the two groups. They also validated their methods in additional individuals, resulting in a total of 1,742 samples from pediatric and adult patients with either new-onset or established disease.
The team found that microbial balance was disrupted in patients with Crohn's disease, with beneficial microbes missing and pathological ones flourishing. Having more of the disease-associated organisms correlated with increasing clinical disease activity. "These findings can guide the development of better diagnostics," says senior author Dr. Ramnik Xavier of Massachusetts General Hospital and the Broad Institute of MIT and Harvard. "More importantly, our study identified specific organisms that are abnormally increased or decreased in disease, which forms a blueprint to develop microbial therapeutics."
When the researchers analyzed the effects of antibiotics, which are sometimes used to treat Crohn's disease symptoms prior to diagnosis, they found that antibiotic usage in children with Crohn's disease could be counterproductive because it causes a loss of good microbes and an increase in pathological ones.
The investigators also examined different approaches for measuring gut microbes in patients and found that the bacterial communities in biopsies taken from rectal tissue served as good indicators of disease, regardless of where a patient was experiencing inflammation along the gastrointestinal tract. "This finding is particularly encouraging because it creates the opportunity to use a minimally invasive approach to collecting patient samples for early disease detection," explains first author Dr. Dirk Gevers of the Broad Institute.