Mount Sinai study investigates per- and polyfluoroalkyl substances and IBD risk

Per- and polyfluoroalkyl substances exposure may play a role in the development of inflammatory bowel disease years before symptoms appear, according to a five-year study supported by a $3.3 million National Institutes of Health grant to researchers at the Icahn School of Medicine at Mount Sinai.

Key Clinical Takeaways:

• Researchers at the Icahn School of Medicine at Mount Sinai received a $3.3 million National Institutes of Health R01 grant to study the link between per- and polyfluoroalkyl substances and future inflammatory bowel disease.
• The study will analyze blood samples collected one to 10 years before diagnosis from active-duty U.S. military service members in the PREDICTS cohort.
• Investigators will measure all detectable per- and polyfluoroalkyl substances and investigate glycosylation changes and intestinal glycocalyx disruption using mass spectrometry and laboratory models.

Icahn School of Medicine Mount Sinai Study Design and Funding

The study investigates whether per- and polyfluoroalkyl substances, frequently called forever chemicals, disrupt biological processes protecting the intestine and regulating the immune system. Previous work by Manasi Agrawal and colleagues showed an association between higher concentrations of per- and polyfluoroalkyl substances mixtures and increased odds of developing inflammatory bowel disease years later. The new research measures all detectable per- and polyfluoroalkyl substances to reflect everyday complex exposures, moving beyond previous studies that focused on only one or a few of these chemicals.

Researchers Analyze Blood Samples from Military Members

Blood specimens gathered through the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects project will undergo testing by investigators.

This cohort includes active-duty U.S. military service members who subsequently developed Crohn’s disease or ulcerative colitis, alongside matched controls. Blood samples were collected at four time points spanning one to 10 years before diagnosis. 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 mass spectrometry analyses to measure per- and polyfluoroalkyl substances exposure.

Glycosylation Alterations and Intestinal Health

The research investigates glycosylation, a biological process adding carbohydrate structures to proteins. Alterations in glycosylation have been documented prior to the onset of inflammatory bowel disease, and this biochemical modification is vital for maintaining normal intestinal health and immune system operations.

The study tests whether per- and polyfluoroalkyl substances exposure contributes to disease by disrupting the protective glycocalyx lining the intestine and altering blood glycosylation patterns. Vishal Midya, assistant professor of environmental medicine and public health, will conduct statistical analyses examining relationships among exposure, biological changes, and disease risk, while complementary laboratory studies examine specialized mouse models.

Research Aims to Identify Individuals at Risk

Manasi Agrawal, associate professor of medicine (gastroenterology), and environmental medicine, and director of environmental gastroenterology at the Icahn School of Medicine, stated that the goal is to better understand how environmental exposures influence the earliest stages of inflammatory bowel disease. By studying exposure and biological changes occurring years before diagnosis, researchers hope to uncover mechanisms helping identify at-risk individuals and inform prevention strategies and personalized care approaches. 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 preceding disease development could provide important insights into how environmental exposures contribute to the condition and potentially point to new opportunities for earlier intervention.

Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.