Study explores how environmental factors increase IBD risk
A recent study identified several environmental chemical agents, including a common herbicide, that may boost gastrointestinal inflammation, increasing the risk of inflammatory bowel disease (IBD).
The study was conducted by researchers at Brigham and Women’s Hospital in Boston, Massachusetts, and published in the journal, Nature. According to the study’s authors, it’s well established that environmental factors are associated with autoimmune and inflammatory disease, however, scientists have struggled to identify how specific chemicals influence inflammation. For this study, investigators sought to reveal the mechanisms behind how certain chemicals contribute to IBD.
To begin the investigation, researchers integrated IBD genetic databases with a large Environmental Protection Agency database. The database, ToxCast, included biochemical data on consumer, industrial, and agricultural products. Scientists then tested the chemicals predicted to modulate inflammatory pathways on a zebrafish IBD model. Using a machine learning algorithm, scientists also identified an additional 20 chemical candidates that likely promote inflammation. Of these chemicals, the study zeroed in on the herbicide, propyzamide, commonly used to control weeds in sport and crop fields.
After further analysis of the herbicide on both zebrafish and mice models, findings indicated that propyzamide interfere with a transcription factor linked to immune regulation known as the aryl hydrocarbon receptor (AHR). Researchers determined that AHR is responsible for suppressing a proinflammatory pathway, the NF-κB-C/EBPβ-driven response, revealing the mechanisms behind how the herbicide leads to increased intestinal inflammation. According to researchers, C/EBPβ, was previously identified as a genetic biomarker for IBD.
These findings, according to the study’s authors, identify how exposure to specific environmental chemicals is associated with gastrointestinal inflammation, which may contribute to new methods of IBD prevention and treatment.
“As we learn more about the environmental factors that might contribute to disease, we can develop state and national level strategies to limit exposures,” said Francisco Quintana, PhD, an investigator in the Brigham’s Ann Romney Center for Neurologic Diseases. “Some chemicals don’t seem to be toxic when tested under basic conditions, but we do not yet know about the effect of chronic, low-level exposures over decades, or early on in development.”