Each of us has a community of bacteria living within our guts. This colony of microorganisms, commonly called the microbiome, weighs up to 3 pounds and performs the often dirty work of breaking down toxins, manufacturing vitamins, and contributing to our immune response. Scientists have long believed features of the microbiome contribute to Crohn’s disease (CD), yet they’ve always lacked proper evidence and specifics. Now, a new study has identified the specific gene profile and microbial community associated with CD, and this profile, the authors believe, may even predict progression of the disease. “Microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches,” note the authors in the conclusion to their research.
Crohn's and other inflammatory bowel diseases have no known cures, yet the symptoms, including abdominal pain, severe diarrhea, and even malnutrition, can be managed with diet and medicine. Generally, the first line of pharmaceutical defense is anti-inflammatory drugs, with antibiotics and immune system suppressors playing a secondary role in treatment strategies. Of necessity, doctors tailor therapies to individual patients as CD generally strikes each person in a unique way. While the Food and Drug Administration is preparing to approve new biologic medications — genetic-based drugs — for Crohn’s, scientists still need to understand more about the microbiome in order to identify which patients will derive the greatest benefit from this new treatment approach.
A major motivation for the current study, then, was learning more about the underlying genetics of Crohn’s disease to better treat patients. Remember: The microbiome is composed of bacteria, each of which has its own DNA. Past patient-based studies have suggested that the final part of the small intestines (the terminal ileum) plays a central role in Crohn’s disease and may be the primary site where disease begins. For this reason, the research team from Cincinnati Children's Hospital Medical Center focused on the ileal microbial community when performing gene analyses on tissue extracted during a patient's first diagnostic endoscopy. In total, the team analyzed and compared samples from 359 people, including patients with Crohn’s disease, patients with ulcerative colitis, and healthy volunteers.
They discovered Crohn's disease patients had altered expression of two genes, DUOX2 and APOA1, as well as a very distinct microbial community. “Furthermore, APOA1 expression and microbial abundance could be used to predict clinical outcomes in Crohn's disease patients,” the authors noted. They believe their research will contribute to patient diagnosis and treatment categorization.
Source: Haberman Y, Tickle TL, Dexheimer PJ, et al. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. Journal of Clinical Investigation. 2014.