Exposure to per- and polyfluoroalkyl substances (PFAS), often called “forever chemicals,” may play a role in the development of inflammatory bowel disease (IBD) years before symptoms appear, suggests a new study led by an Indian American researcher.

The five-year study led by Manasi Agrawal, Associate Professor of Medicine (Gastroenterology), and Environmental Medicine, and Director of Environmental Gastroenterology at the Icahn School of Medicine at Mount Sinai, is supported by a $3.3 million National Institutes of Health (NIH) R01 grant.

It will investigate whether PFAS’ exposure disrupts biological processes that protect the intestine and regulate the immune system, potentially increasing the risk of IBD.

The research builds on previous work by Dr. Agrawal and colleagues showing an association between higher concentrations of PFAS mixtures and increased odds of developing IBD years later.

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Unlike previous studies that have focused on one or a few PFAS chemicals, the new study will measure all detectable PFAS chemicals to better reflect the complex exposures people experience in everyday life.

The researchers will also investigate glycosylation, a biological process that adds carbohydrate structures to proteins. Glycosylation plays an important role in intestinal health and immune function, and changes in glycosylation have been observed before IBD develops.

The study will test whether PFAS exposure may contribute to IBD by disrupting the protective glycocalyx that lines the intestine and altering glycosylation patterns in the blood.

“Our goal is to better understand how environmental exposures may influence the earliest stages of inflammatory bowel disease,” said Dr. Agrawal. “By studying PFAS exposure and the biological changes that occur years before diagnosis, we hope to uncover mechanisms that could help identify individuals at risk and ultimately inform prevention strategies and more personalized approaches to care.”

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Researchers will analyze blood samples from the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study, a cohort of active-duty U.S. military service members that includes individuals who subsequently developed Crohn’s disease or ulcerative colitis and matched controls. Blood samples were collected at four time points, spanning 1-10 years before diagnosis, allowing researchers to examine environmental exposures and biological changes that precede disease.

Dr. Agrawal graduated from Gandhi Medical College, India, with academic distinctions and received the Indian Council of Medical Research scholarship. She trained in Internal Medicine at Maimonides Medical Center, Brooklyn and in Gastroenterology at Montefiore Medical Center, Albert Einstein College of Medicine in the Bronx.

She completed advanced fellowships in IBD at Lenox Hill Hospital Northwell Health and at the Icahn School of Medicine at Mount Sinai. She completed Masters in Biostatistics and the Career MODE Program at Columbia University, Mailman School of Public Health, New York.