Weed killer may raise risk of inflammatory bowel disease: study

Exposure to a common weed killer may boost inflammation in the small and large intestine, raising the risk of developing inflammatory bowel disease, a new study has found.

Scientists singled out the herbicide — called propyzamide — after leveraging multiple research platforms to identify chemical agents in the environment that might influence gastrointestinal inflammation, according to the study, published on Thursday in Nature.

“Environmental factors are known to be just as important as genetic factors in influencing autoimmune and inflammatory disease,” corresponding author Francisco Quintana, an investigator at Brigham and Women’s Hospital’s Ann Romney Center for Neurologic Diseases, said in a statement.

“Yet we lack a method or platform to systematically identify the effect of chemical candidates on inflammation,” added Quintana, whose lab has previously investigated environmental impacts on neurodegeneration, the loss of function of neurons.

Quintana and his colleagues integrated inflammatory bowel disease databases with an Environmental Protection Agency index called ToxCast, which includes biochemical data on consumer, industrial and agricultural products.

After identifying chemicals that might influence inflammatory pathways, they worked with a zebrafish model to test the compounds and their effects on inflammation.

Scientists often use zebrafish — a freshwater fish in the minnow family — as a model organism because their genome is fully sequenced and they undergo rapid development.

The researchers also said they employed a machine learning algorithm to pinpoint additional chemicals in the ToxCast database that would likely cause inflammation.

Out of the top 20 candidate compounds — 11 of which are used in agriculture — the scientists then narrowed down their focus to propyzamide.

Marketed under a variety of brand names, propyzamide is commonly applied to sports fields and fruit and vegetable crops to manage weeds, the authors noted.

During subsequent cell-culture, zebrafish and mouse studies, the researchers found that propyzamide interferes with a specific protein involved in immune regulation.

That protein maintains gut stability by suppressing a second, pro-inflammatory pathway, according to the study.

“Our methodology allowed us to identify a chemical that disrupts one of the body’s natural ‘brakes’ on inflammation,” Quintana said.

Yet because their approach also unmasked certain mechanisms that regulate autoimmune responses, the technique could also be used to help design therapeutic anti-inflammatory drugs down the line, according to Quintana.

The researchers said they are therefore working to engineer nanoparticles and probiotics capable of targeting the inflammatory pathway that they identified.

“As we learn more about the environmental factors that might contribute to disease, we can develop state- and national-level strategies to limit exposures,” Quintana said. 

“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,” he added.