AI Research: Exploring the Potential Connection Between PFAS Substances and Eosinophilic Esophagitis

AI Research: Exploring the Potential Connection Between PFAS Substances and EoE

Abstract

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used for their resistance to heat, water, and oil. Due to their persistence in the environment, PFAS have been associated with various health issues, including immune system modulation. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease characterized by eosinophil infiltration. This paper reviews existing literature to explore the potential connection between PFAS exposure and the development or exacerbation of EoE. While direct studies are limited, evidence suggests that PFAS-induced immune dysregulation could contribute to the pathogenesis of EoE, warranting further research in this area.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by symptoms related to esophageal dysfunction and histological evidence of eosinophil-predominant inflammation (Dellon et al., 2018). The incidence of EoE has been increasing globally, suggesting potential environmental factors in its etiology (Liacouras et al., 2011).

Per- and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals used in various industrial applications and consumer products, such as non-stick cookware, stain-resistant fabrics, and firefighting foams (United States Environmental Protection Agency [USEPA], 2022). PFAS are persistent in the environment and bioaccumulate in human and animal tissues, leading to widespread exposure (Sunderland et al., 2019).

Given the immunomodulatory effects of PFAS and the immune-mediated nature of EoE, this paper explores the potential connection between PFAS exposure and EoE development.

Background

PFAS and Human Health

PFAS are known to interfere with immune system function. Studies have linked PFAS exposure to altered immune responses, reduced vaccine efficacy, and increased susceptibility to infections (Grandjean & Clapp, 2015; DeWitt et al., 2019). PFAS can affect both humoral and cellular immunity, potentially leading to dysregulated immune responses.

Eosinophilic Esophagitis (EoE)

EoE is characterized by eosinophil infiltration in the esophageal epithelium, leading to chronic inflammation and esophageal dysfunction (Furuta et al., 2007). The pathogenesis of EoE involves a complex interplay between genetic predisposition, environmental factors, and immune responses, particularly Th2-mediated hypersensitivity reactions to food and aeroallergens (Hirano et al., 2019).

Potential Mechanisms Linking PFAS to EoE

Immune System Modulation

PFAS exposure has been associated with alterations in cytokine production and immune cell function. For instance, PFAS can enhance Th2 cytokine responses, which are implicated in allergic diseases (Corsini et al., 2014). Th2 cytokines, such as interleukin-5 (IL-5), play a critical role in eosinophil activation and survival, key features in EoE pathogenesis (Blanchard et al., 2006).

Allergic Sensitization

Studies have indicated that PFAS exposure may increase the risk of developing allergic conditions. A cross-sectional study found that higher PFAS levels were associated with increased odds of asthma and allergic sensitization in children (Dong et al., 2013). Since EoE is often associated with allergic sensitizations, PFAS-induced allergic propensity could contribute to EoE development.

Epithelial Barrier Dysfunction

PFAS may disrupt epithelial barrier integrity, leading to increased permeability and antigen penetration. Although research has primarily focused on the gut epithelium, similar mechanisms in the esophagus could facilitate allergen exposure to the immune system, promoting eosinophilic inflammation (Jeong et al., 2020).

Evidence from Epidemiological Studies

Direct epidemiological studies examining the association between PFAS exposure and EoE are currently lacking. However, the rising incidence of EoE parallels increased PFAS contamination in the environment, suggesting a possible temporal relationship that warrants investigation (Holm et al., 2022).

Discussion

The immunomodulatory effects of PFAS provide a plausible biological mechanism linking PFAS exposure to EoE. PFAS-induced enhancement of Th2 responses and eosinophil activation could contribute to the development or exacerbation of EoE. Additionally, PFAS-related epithelial barrier dysfunction may facilitate allergen exposure, further promoting eosinophilic inflammation.

Limitations

Lack of Direct Evidence: There is a paucity of studies directly linking PFAS exposure to EoE.
Confounding Factors: Environmental and genetic factors influencing EoE and PFAS exposure may confound potential associations.
Variability in Exposure Assessment: Differences in PFAS exposure measurement across studies hinder comparisons and meta-analyses.

Future Directions

Epidemiological Studies: Longitudinal cohort studies assessing PFAS exposure and EoE incidence are needed to establish temporal and causal relationships.
Mechanistic Research: In vitro and animal studies investigating PFAS effects on esophageal epithelial cells and immune responses can elucidate underlying mechanisms.
Public Health Interventions: Reducing PFAS exposure through regulatory policies and public awareness may mitigate potential health risks.

Conclusion

While direct evidence is limited, existing research suggests that PFAS exposure could contribute to the pathogenesis of EoE through immune modulation and barrier dysfunction. Given the widespread exposure to PFAS and the increasing prevalence of EoE, further research is essential to clarify this potential connection and inform public health strategies.

References

Blanchard, C., Wang, N., Stringer, K. F., Mishra, A., & Collins, M. H. (2006). Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. Journal of Clinical Investigation, 116(2), 536–547.
Corsini, E., Luebke, R. W., Germolec, D. R., & DeWitt, J. C. (2014). Perfluorinated compounds: emerging POPs with potential immunotoxicity. Toxicology Letters, 230(2), 263–270.
Dellon, E. S., Liacouras, C. A., Molina-Infante, J., et al. (2018). Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology, 155(4), 1022–1033.
DeWitt, J. C., Patisaul, H. B., & Zoeller, R. T. (2019). Endocrine disrupting chemicals: implications for risk assessment. Environment International, 128, 1–3.
Dong, G. H., Tung, K. Y., Tsai, C. H., et al. (2013). Serum perfluorinated chemicals, glutathione S-transferase polymorphisms, and asthma-related outcomes in children. American Journal of Respiratory and Critical Care Medicine, 188(4), 389–395.
Furuta, G. T., Liacouras, C. A., Collins, M. H., et al. (2007). Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology, 133(4), 1342–1363.
Grandjean, P., & Clapp, R. (2015). Perfluorinated alkyl substances: emerging insights into health risks. New Solutions: A Journal of Environmental and Occupational Health Policy, 25(2), 147–163.
Hirano, I., Chan, E. S., Rank, M. A., et al. (2019). AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Annals of Allergy, Asthma & Immunology, 123(5), 450–461.
Holm, S. M., Leonard, S. S., & Kyser, S. (2022). Evolving concerns regarding per- and polyfluoroalkyl substances (PFAS). Journal of Environmental Health, 84(6), 28–31.
Jeong, S., Lim, J., Choi, Y., & Kim, H. (2020). Perfluorooctanoic acid induces gut inflammation through Th17 activation. Scientific Reports, 10(1), 1–11.
Liacouras, C. A., Furuta, G. T., Hirano, I., et al. (2011). Eosinophilic esophagitis: updated consensus recommendations for children and adults. Journal of Allergy and Clinical Immunology, 128(1), 3–20.
Sunderland, E. M., Hu, X. C., Dassuncao, C., et al. (2019). A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects. Journal of Exposure Science & Environmental Epidemiology, 29(2), 131–147.
United States Environmental Protection Agency (USEPA). (2022). PFAS Explained. Retrieved from https://www.epa.gov/pfas/pfas-explained