NYCU Work with Harvard University to Discover Herbicides as a Stimulation of Immune Responses Intestinal Inflammation

Dr. Yu-Chao Wang and his research team.

Intestinal inflammation has become increasingly prevalent in Taiwan due to genetic inheritance and western food consumption. The research team of National Yang Ming Chiao Tung University (NYCU) and Harvard University has discovered herbicides as a potential risk factor that deteriorates such inflammation. This discovery marks a breakthrough regarding the effect of environmental factors on inflammatory bowel disease (IBD) and has therefore been published in Nature.

IBD mainly includes ulcerative colitis and Crohn’s disease. The diagnosed ulcerative colitis rate in Taiwan increased from 2.1 patients per 100,000 in 2001 to 12.8 patients per 100,000 in 2015. This is a five-times increase within 14 years [1]. In the past, IBD was mainly discovered in Western countries. Although scholars have confirmed approximately 200 genes that can be related to this type of disease, their understanding of relevant environmental factors is still limited.

Associate Professor Yu-Chao Wang from the Institute of Biomedical Informatics, NYCU, collaborated with Harvard Medical School to analyze the possible factors of IBD. They used zebrafish to examine chemical substances potentially affecting intestinal inflammation and created a prediction model for compounds that deteriorate IBD. The model was applied to the ToxCast database of the US Environmental Protection Agency to identify more compounds that may lead to the deterioration of IBD.

Among the top 20 most influential compounds identified by Dr. Wang, over half of them were associated with agriculture. The research team examined propyzamide, a type of herbicide commonly used to remove weeds in sports venues and gardens, by conducting in vitro and in vivo experiments. They further confirmed that this compound disturbs dioxin receptors that maintain intestinal stability and induces immune responses associated with T cells and dendritic cells, thereby causing the deterioration of IBD.

Propyzamide decomposes slowly when used on plants, and 60% of the compound can remain on plants even after 50 days. Consequently, individuals who frequently walk or exercise in grass sports fields or gardens risk being exposed to propyzamide. In response to the result, the team is currently developing nanoparticles and probiotics to alleviate IBD caused by herbicides.

This research project involves interdisciplinary efforts from both dry labs and wet labs. Dry labs generally focus on computer simulation, whereas wet labs mainly conduct conventional biochemistry analysis. In the current research collaboration between Taiwan and the United States, the NYCU research team uses big data from relevant databases to create disease prediction models. The Harvard research team, led by Dr. Francisco Quintana, then verifies the models using conventional laboratory techniques and large samples.

Dr. Wang noted that interdisciplinary research is a common and crucial biomedical approach that has been prevalently applied in researching various diseases. Bioinformatics involves extensive data analysis to quickly identify potential treatment methods, which are verified through laboratory experiments. This reduces the substantial human resources, time consumption, and costs required in conventional biological research. The research team’s finding caught the attention of Nature, for it identified an environmental factor of IBD and demonstrated the viability of combining bioinformatics with in vitro and in vivo experiments through interdisciplinary collaboration.

Dr. Francisco Quintana(left) from Harvard Medical school and Dr. Yu-Chao Wang(right) from NYCU.

[1] Yen et al. (2019). Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide population based study. Intestine Research, 17(1).