Depression Mediates the Association Between Ambient Air Pollution and Gastrointestinal/Liver Diseases: A Prospective Cohort Study

ABSTRACT Background The escalating burden of gastrointestinal (GI) and liver diseases poses a critical public health challenge, with emerging evidence implicating air pollution as a modifiable risk factor. However, the mechanistic pathways, particularly the mediating role of depression in the pollution‐disease nexus, remain underexplored. This study investigates the longitudinal associations between ambient air pollution exposure and GI/liver diseases in a nationwide cohort, with a focus on quantifying depression's mediating effects. Methods Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020; n = 18,755), we evaluated the impact of long‐term exposure to PM 1 , PM 2.5 , PM 10 , SO 2 , CO, NO 2 , and O 3 on incident GI/liver diseases. Multivariable‐adjusted Cox proportional hazards models incorporated demographic, socioeconomic (region, education, retirement status), and lifestyle (smoking, drinking) covariates. Mediation analysis assessed the proportion of total effects mediated by depression (CESD‐10 scores). Results Chronic exposure to PM 1 (HR = 1.33, 95% CI: 1.30–1.37), PM 2.5 (HR = 1.30, 1.26–1.33), PM 10 (HR = 1.29, 1.25–1.32), SO 2 (HR = 1.64, 1.60–1.69), CO (HR = 1.47, 1.43–1.51), and NO 2 (HR = 1.27, 1.23–1.30) per interquartile range increase was significantly associated with elevated disease risk, whereas O 3 exhibited protective effects (HR = 0.77, 0.74–0.79). Depression mediated 4.0%–11.3% of pollution effects, with the highest mediation observed for O 3 (11.3%) and lowest for SO 2 (4.0%). Stratified analyses revealed heightened vulnerability in rural residents, individuals with lower education, and Northeastern populations. Conclusions This study pioneers the identification of depression as a mediator linking air pollution to GI/liver diseases in a nationally representative cohort. The findings advocate for integrative policies targeting air quality improvement and mental health interventions to alleviate the dual burden of environmental and psychological morbidity.