Exposure to per- and polyfluoroalkyl substances, widely known as PFAS or “forever chemicals,” may play a role in the development of inflammatory bowel disease years before clinical symptoms emerge. A new five-year investigation funded by a $3.3 million National Institutes of Health R01 grant aims to track these environmental toxins at the Icahn School of Medicine at Mount Sinai.
Tracking Forever Chemicals Before IBD Diagnosis
The research project builds directly on prior findings led by Dr. Manasi Agrawal, which linked higher concentrations of PFAS mixtures in the blood to increased odds of developing inflammatory bowel disease later in life. While earlier scientific literature typically examined one or a few PFAS chemicals, the new Mount Sinai study will measure all detectable PFAS chemicals. This comprehensive approach mirrors the complex exposures people encounter in everyday life.
Investigators will analyze blood samples drawn from the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects, known as the PREDICTS study. This cohort comprises active-duty U.S. military service members who eventually developed Crohn’s disease or ulcerative colitis, alongside matched control participants. Because the repository holds blood samples gathered across four distinct time points spanning one to ten years prior to an actual diagnosis, researchers can examine environmental exposures and biological changes that precede disease.
Disrupting the Intestinal Protective Barrier
The research team will examine glycosylation, a biological process that attaches carbohydrate structures to proteins to support intestinal health and immune regulation. Changes in glycosylation have been observed before inflammatory bowel disease manifests in patients. Scientists will test whether exposure to PFAS contributes to IBD by damaging the protective glycocalyx lining the intestine while simultaneously shifting glycosylation patterns observed in the blood.
Laboratory experiments using specialized mouse models will run parallel to the human cohort analyses. These tests will evaluate how PFAS exposure alters the intestinal glycocalyx, disrupt normal glycosylation, and affect intestinal inflammation. Dr. Jean-Frederic Colombel, Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai and Principal Investigator of the PREDICTS study, noted that examining biological changes that precede disease development could provide important insights into how environmental exposures contribute to IBD and potentially point to new opportunities for earlier intervention.
Mass spectrometry and statistical evaluations drive laboratory work
Advanced mass spectrometry will drive the chemical detection work inside the laboratory. Dr. Lauren Petrick, 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, will oversee the mass spectrometry operations required to measure all detectable PFAS compounds and map blood glycosylation profiles.
Statistical evaluations will follow the laboratory testing phase. Dr. Vishal Midya, Assistant Professor of Environmental Medicine and Public Health, will conduct statistical analyses to examine relationships among PFAS exposure, biological changes, and IBD risk and disease complications noted at the time of diagnosis. The overarching grant, formally titled “Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure and Glycosylation Alterations Preceding Inflammatory Bowel Disease,” aims to identify biological markers that could eventually help assess risk, inform prevention strategies, and support more individualized treatment.
Active-duty military samples provide data years before diagnosis
What specific group of people provides the blood samples for this study?
Active-duty U.S. military service members enrolled in the PREDICTS study provide the biological samples, including individuals who later developed Crohn’s disease or ulcerative colitis and matched control participants.
How far in advance of an IBD diagnosis are the blood samples collected?
The repository contains blood samples gathered across four distinct time points spanning from one to ten years prior to the clinical diagnosis of inflammatory bowel disease.
What biological mechanism is suspected of linking PFAS exposure to IBD?
Researchers are investigating whether PFAS exposure disrupts glycosylation processes and damages the protective glycocalyx lining that shields the intestine and regulates immune function years before symptoms appear.
Who is leading the research team at Mount Sinai?
Dr. Manasi Agrawal, Associate Professor of Medicine (Gastroenterology) and Environmental Medicine and Director of Environmental Gastroenterology at the Icahn School of Medicine at Mount Sinai, leads the investigation.
How much funding supports this five-year research initiative?
The National Institutes of Health awarded a $3.3 million R01 grant to back the investigation titled “Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure and Glycosylation Alterations Preceding Inflammatory Bowel Disease.”