Common weedkiller may trigger this disease

By Stephen Beech via SWNS

A common weedkiller may trigger inflammatory bowel disease, suggests a new study.

The discovery could revolutionize the treatment of other autoimmune diseases such as multiple sclerosis and type 1 diabetes, scientists say.

The research team identified environmental factors that promote gastrointestinal inflammation using state-of-the-art technology.

Inflammatory bowel disease (IBD), a condition characterized by chronic gastrointestinal inflammation, is becoming increasingly common in industrialized countries.

While researchers have identified around 200 genetic tags associated with the disease, there is a limited understanding of the specific environmental factors that influence the risk and severity of IBD.

The new study, by researchers at Brigham and Women’s Hospital, used various approaches to systematically identify environmental chemical agents that influence gastrointestinal inflammation.

Their findings, published in the journal Nature, identified the common herbicide, propyzamide, that may boost inflammation in the small and large intestines.

Corresponding author Professor Francisco Quintana, of Brigham’s Ann Romney Centre for Neurologic Diseases, said: “Environmental factors are known to be just as important as genetic factors in influencing autoimmune and inflammatory disease, yet we lack a method or platform to systematically identify the effect of chemical candidates on inflammation.

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

"This method can identify new chemical candidates for epidemiological studies, as well as novel mechanisms that regulate autoimmune responses.

"In addition, this platform can also be used to screen and design for therapeutic anti-inflammatory drugs."

The researchers conducted their work by integrating IBD genetics databases with a large Environmental Protection Agency database, ToxCast, which includes biochemical data on consumer, industrial, and agricultural products.

They identified chemicals predicted to modulate inflammatory pathways and then used a novel zebrafish IBD model to test the compounds and determine whether they improve, worsen, or did not affect gut inflammation.

The research team then used a machine learning algorithm trained on the studied compounds to identify additional chemicals in the ToxCast database likely to promote inflammation.

Of the top 20 candidates, 11 of which are used in agriculture, the researchers chose to further examine propyzamide, which is commonly applied to sports fields and fruit and vegetable crops to control weeds.

In subsequent cell culture, zebrafish and mouse studies, the researchers showed that propyzamide interferes with the aryl hydrocarbon receptor (AHR), a transcription factor that Quintana first reported in 2008 to be involved in immune regulation.

The new study outlines the specific mechanism by which the genetic biomarker leads to increased intestinal inflammation.

Now the research team is working to engineer nanoparticles and probiotics that can target the inflammatory pathway they have identified.

The US Food and Drug Administration recently approved a topical cream for psoriasis, called tapinarof, which functions by activating the anti-inflammatory AHR pathway, raising the possibility that a similar drug for IBD may be able to be developed by taking advantage of this mechanism.

Quintana explained that the activation of the AHR pathway may also be relevant for the treatment of other autoimmune diseases such as multiple sclerosis and type 1 diabetes, which are mediated by similar immune cells.

He added: “The anti-inflammatory AHR pathway we identified could be strengthened to ameliorate disease.

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

"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.”