Exposure to per- and polyfluoroalkyl substances and inflammatory bowel disease: review and meta-analysis

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are stable chemicals that are well preserved in the environment and persist in the human body. PFAS have been associated with inflammatory bowel disease (IBD), but studies are varied in their findings. Objective The objective of this study was to conduct a review of the literature and meta-analysis evaluating PFAS exposure and IBD. Methods PubMed, SCOPUS, Cochrane Library, and the Web of Science were searched for original research articles published in English between 1980 and July 2023 and with human subjects. An adapted risk of bias grading chart was created a priori in order to assess the risks of bias relevant to the studies. For each health outcome, the relative risk point estimates and confidence intervals were used in the synthesis of results. Results Six studies were identified and assessed for risk of bias. Using random effects meta-analysis for the four studies reporting odds ratios and confidence intervals for serum PFAS concentrations, we found that the average relative increase in ulcerative colitis per 1 ng/mL increase in measured or modeled serum PFOA for these studies is 7% (95% CI: –4.7%, 20.0%). For other PFAS chemicals, there were only three or fewer studies reporting odds ratios for PFAS and IBD. Significance Our results indicate that there is an increased risk of developing ulcerative colitis with increasing serum PFOA; however, the effect is not statistically significant, and has substantial uncertainty. Further research and studies are warranted to enhance the precision of these estimates and clarify the nature of this association. Impact This literature review and meta-analysis evaluate the epidemiologic evidence linking PFAS exposure to irritable bowel disease (IBD)—specifically ulcerative colitis and Crohn’s disease. Results were heterogeneous, and meta-analyses yielded null findings across all PFAS-outcome pairs. Risk of bias due to exposure misclassification, reverse causation, and inadequate control sampling limited confidence in the findings. These results highlight the need for future research and rigorously designed studies to evaluate PFAS as environmental risk factors for IBD.