New study investigates PFAS exposure and future inflammatory bowel disease

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, according to a new five-year study supported by a $3.3 million National Institutes of Health (NIH) R01 grant to researchers at the Icahn School of Medicine at Mount Sinai.

The study, led by Manasi Agrawal, MD, MS, Associate Professor of Medicine (Gastroenterology), and Environmental Medicine, and Director of Environmental Gastroenterology at the Icahn School of Medicine, 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. 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.

The study will examine:

• Whether individual PFAS chemicals and PFAS mixtures are associated with future IBD risk and complications at diagnosis
• Whether PFAS exposure is associated with changes in blood glycosylation patterns before IBD develops
• Whether changes in glycosylation are associated with future development of Crohn's disease or ulcerative colitis
• How PFAS exposure affects the intestinal glycocalyx, glycosylation, and intestinal inflammation in laboratory models

Dr. Manasi Agrawal, MD, MS, Associate Professor of Medicine (Gastroenterology), and Environmental Medicine, and Director of Environmental Gastroenterology, Icahn School of MedicineOur goal is to better understand how environmental exposures may influence the earliest stages of inflammatory bowel disease. 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."

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.

Other Mount Sinai investigators contributing to the study include Lauren Petrick, PhD, Professor of Environmental Medicine and Head of Untargeted Metabolomics at the Senator Frank R. Lautenberg Environmental Health Sciences Laboratory at the Icahn School of Medicine at Mount Sinai, who will oversee the mass spectrometry analyses to measure PFAS exposure; and Vishal Midya, PhD, MStat, Assistant Professor of Environmental Medicine, and Public Health, who will conduct statistical analyses to examine relationships among PFAS exposure, biological changes, and IBD risk.

Using mass spectrometry, investigators will measure all detectable PFAS chemicals and characterize glycosylation profiles in the blood samples. Complementary laboratory studies will examine how PFAS exposure affects the intestinal glycocalyx, glycosylation, and inflammation in specialized mouse models.

"By examining biological changes that precede disease development, this research could provide important insights into how environmental exposures contribute to IBD and potentially point to new opportunities for earlier intervention," said Jean-Frederic Colombel, MD, Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, and Principal Investigator of the PREDICTS study.

The researchers hope the findings will clarify how PFAS exposure may contribute to IBD and identify biological markers that could eventually help assess risk, inform prevention strategies, and support more individualized treatment.

The grant title is "Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure and Glycosylation Alterations Preceding Inflammatory Bowel Disease."

Source:

Mount Sinai Health System