Sometimes, patients’ genetic profiles lead to diseases such as Crohn’s and other inflammatory bowel diseases. Other times the environment impacts disease onset. Often, the two factors combine, and a study from Lee Denson and colleagues at Cincinnati Children’s Hospital Medical Center published in Journal of Clinical Investigation looked at the interaction of genes, gut microbiota, and environmental cues in promoting Crohn’s disease.
Dr. Denson’s study, written by lead author Yael Haberman and other researchers from institutions across the United States and Canada, looked at 359 Crohn’s patients who had never had been treated, ulcerative colitis patients, and healthy participants. Gene expression profiles and the microbial community of the ileum, which is the last of the three segments of the small intestine, were compared among individuals.
A specific signature was characteristic to Crohn’s patients unique from ulcerative colitis patients and healthy participants and independent of clinical inflammation. Expression of lipoprotein APOA1 was lower in Crohn’s patients and associated with alterations in Firmicutes, a type of bacteria.
In addition, abnormally high levels of antimicrobial dual oxidase (DUOX2) gene expression were found in both Crohn’s and ulcerative colitis patients. The combination of decreased APOA1 and increased DUOX2 led to enhanced oxidative stress and a tendency for macrophage cell polarization to Th1 (pro-inflammatory), especially in patients with more severe mucosal injury.
In terms of microbiota, Proteobacteria were expanded in both ulcerative colitis and Crohn’s. Impressively, when microbial abundance and APOA1 gene expression were included in a regression model, six month steroid-free remission was more accurately predicted than when a model based on clinical factors alone was used.
The authors concluded that, “These Crohn’s Disease-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of Crohn’s Disease and may direct prognostic and therapeutic approaches.”