Dietary Exposure to PFAS: Gut Toxicity as a Gateway to Systemic Health Effects

Per- and polyfluoroalkyl substances (PFAS), known as "forever chemicals," are persistent global contaminants that infiltrate the agricultural food chain (e.g., concentrations of 0.159 ng/g have been measured in leafy vegetables such as lettuce), as shown by Piva et al. (2023). By extension, these chemicals pose a significant threat to human health. This review synthesizes current evidence to identify the pathway from environmental PFAS contamination to adverse health outcomes with a specific focus on the gastrointestinal tract as the critical gateway for dietary exposure. It examines how PFAS enter the environment, via industrial discharge, biosolids, and atmospheric deposition, and are taken up by crops, with uptake varying by PFAS type and crop. In one study, the mean total PFAS concentration in ready-to-eat leafy vegetable produces reached 0.13 ng/g (SD 0.09), compared with 0.07 ng/g (SD 0.07) for fresh vegetables and 0.06 ng/g (SD 0.05) for frozen vegetables, indicating clear variability in PFAS levels by processing category (Piva et al., 2023). Upon ingestion, PFAS disrupt the gut barrier and microbiome, promoting a state of chronic inflammation. This gut-level pathology is mechanistically linked to systemic effects, including immunosuppression, endocrine disruption, and metabolic disease. This review further highlights distinct exposure vulnerabilities, with rural populations often facing higher risks from point sources and urban populations being exposed to complex mixtures from commercial foods and packaging. Finally, we identify critical knowledge gaps, such as the need for long-term studies on chronic exposure and a better understanding of PFAS mixture toxicity, and emphasize the crucial need for integrated mitigation strategies that span agricultural management, technological innovation, and robust regulatory policy to address this pervasive public health challenge.