NIH-funded study probes PFAS and pre-diagnostic changes in IBD

The National Institutes of Health has awarded a $3.3 million R01 grant to researchers at the Icahn School of Medicine at Mount Sinai to investigate whether exposure to per- and polyfluoroalkyl substances, commonly known as PFAS or “forever chemicals,” is associated with biological changes that precede inflammatory bowel disease. The five-year project will combine analysis of blood samples from a military cohort with laboratory studies of intestinal biology. It is a planned research program, and the grant announcement does not report results showing that PFAS cause Crohn’s disease or ulcerative colitis.

Manasi Agrawal, MD, MS, will lead the study. The investigator is an associate professor of medicine in gastroenterology and environmental medicine and directs environmental gastroenterology at the Icahn School of Medicine. The research will focus on whether PFAS exposure is related to disrupted processes that protect the intestine and regulate the immune system, potentially providing a pathway through which environmental exposure could be associated with IBD risk.

The grant is titled “Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure and Glycosylation Alterations Preceding Inflammatory Bowel Disease.” The project builds on previous work by Agrawal and colleagues that found an association between higher concentrations of PFAS mixtures and increased odds of developing IBD years later. The new study extends that line of inquiry by measuring all detectable PFAS chemicals rather than focusing on one or a few compounds.

Investigators plan to examine whether individual chemicals and PFAS mixtures are associated with future IBD risk and with complications present at diagnosis. Those are prospective questions within the study’s design, not established outcomes of the grant-supported project. A central part of the work is glycosylation, a biological process that adds carbohydrate structures to proteins.

The announcement says glycosylation is important to intestinal health and immune function, and changes in glycosylation have been observed before IBD develops. Researchers will test whether PFAS exposure is associated with changes in blood glycosylation patterns before disease and whether those changes are associated with the later development of Crohn’s disease or ulcerative colitis. The analysis will keep these relationships distinct: the project will examine exposure, pre-diagnostic molecular changes and subsequent disease without assuming that an observed association proves causation.

The human component will use blood samples from the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects, known as PREDICTS. The cohort consists of active-duty U.S. military service members and includes people who subsequently developed Crohn’s disease or ulcerative colitis, along with matched controls. Samples were collected at four time points spanning one to 10 years before diagnosis.

This design gives researchers access to blood specimens and exposure information from periods before disease was diagnosed, allowing them to examine whether PFAS measurements and glycosylation patterns were associated with later outcomes. Investigators will use mass spectrometry to measure all detectable PFAS chemicals and characterize glycosylation profiles in the blood samples. Lauren Petrick, PhD, professor of environmental medicine and head of the Untargeted Metabolomics group at the Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, will oversee the mass-spectrometry analyses used to measure PFAS exposure.

Vishal Midya, PhD, MStat, assistant professor of environmental medicine and public health, will conduct the statistical analyses of relationships among PFAS exposure, biological changes and IBD risk. Their work will assess both individual PFAS chemicals and mixtures within the available cohort samples. Complementary experiments will use specialized mouse models to examine how PFAS exposure affects the intestinal glycocalyx, glycosylation and inflammation.

The glycocalyx is a protective layer lining the intestine. The investigators plan to assess whether PFAS exposure produces changes in that layer, in glycosylation patterns and in intestinal inflammation under laboratory conditions. The announcement describes these experiments as a way to investigate biological processes that may connect PFAS exposure with intestinal and immune regulation.

Agrawal said the project’s goal is to better understand how environmental exposures may influence the earliest stages of inflammatory bowel disease. By studying PFAS exposure and biological changes occurring years before diagnosis, the researchers hope to uncover mechanisms that could eventually help identify individuals at risk and inform prevention strategies and more personalized approaches to care. The announcement also describes the possibility that the work could point to biological markers for assessing risk.

These remain stated objectives: the study has not yet identified a validated biomarker, demonstrated a prevention strategy or established a new treatment. The grant announcement provides a research plan rather than peer-reviewed findings from the new project. It does not report how many participants will be included in the analyses, the expected effect size of any PFAS–IBD association, or the degree to which the observed patterns will differ between Crohn’s disease and ulcerative colitis.

Nor does it establish whether any pre-diagnostic glycosylation signature can predict disease in people outside the cohort. The researchers will examine associations involving future disease risk and complications at diagnosis, but the incidence, magnitude and clinical importance of those associations will remain unknown until the study is completed and the results are available. The population also defines an important scope for interpretation.

PREDICTS includes active-duty U.S. military service members, so the analysis concerns exposure and disease patterns within that group. Results may not automatically represent people with different occupational, residential or environmental exposures elsewhere. For now, the study’s purpose is to test a specific set of relationships among PFAS exposure, glycosylation, intestinal biology and later IBD, rather than to announce a demonstrated cause, clinical test or preventive intervention.

Subject of Research: PFAS exposure, pre-diagnostic glycosylation and inflammatory bowel disease

Article Title: NIH awards Mount Sinai researcher $3.3 million to study how “forever chemicals” may contribute to IBD

Article References: NIH awards Mount Sinai researcher $3.3 million to study how “forever chemicals” may contribute to IBD. Original publication (Bibliographic details unavailable.)

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DOI: Not provided

Keywords: PFAS, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, glycosylation, glycocalyx, environmental health, mass spectrometry, military cohort, Mount Sinai, awards, Mount