The research, led by Peng Hu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, adds new biological insight into how environmental exposures may contribute to gout, a common inflammatory arthritis traditionally associated with genetics, diet, and metabolic health. By focusing on metabolomic changes—small molecules that reflect biochemical activity in the body—the study moves beyond exposure alone to explore possible mechanistic pathways.
Investigators analyzed data from more than 207,000 adults who were free of gout at baseline and followed them for a median of 12.6 years. During this period, 2,474 participants developed gout. Annual exposure to major air pollutants—including fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx)—was estimated based on participants’ residential addresses using validated modeling methods.
To identify metabolic patterns linked to pollution exposure, the researchers applied elastic net regression, a machine-learning approach well suited to high-dimensional metabolomics data.
The following were the key findings:
- The analysis identified multiple metabolites linked to long-term exposure to air pollutants, forming distinct metabolic signatures for each pollutant, including 87 metabolites for PM2.5, 76 for PM10, 68 for NO2, and 71 for NOx.
- Higher air pollution–related metabolic signature scores were consistently associated with an increased risk of developing gout.
- Across different pollutants, hazard ratios ranged from 1.09 to 1.12, indicating a 9% to 12% higher gout risk among individuals with stronger metabolic signatures of pollution exposure.
- Direct analysis of pollution exposure showed that each interquartile range increase in PM2.5 and PM10 was associated with a 17% and 15% higher risk of gout, respectively.
- Similar increases in NO2 and NOx exposure were linked to a 6% rise in gout risk.
- These findings add to evidence that air pollution may contribute to metabolic and inflammatory diseases, beyond its established role in cardiovascular and respiratory conditions.
- Mediation analyses suggested that metabolomic alterations partially explained the association between air pollution and gout.
- Although the proportion mediated was modest, ranging from approximately 2% to 4% depending on the pollutant, the results indicate that pollution-related metabolic disruption may play an active role in gout development rather than serving only as a marker of exposure.
The authors noted that identifying metabolic signatures provides a potential biological bridge between environmental exposures and gout risk. While further studies are needed to confirm causality and explore clinical implications, the findings highlight air pollution as a potentially modifiable risk factor and underscore the value of metabolomics in uncovering early biological effects of environmental hazards.
Reference:
Hu, P., Wei, S., Ran, S., Zheng, D., Tian, F., Chen, L., Rao, M., Ai, Z., Huang, Z., & Lin, H. Characterizing metabolic signatures of air pollution and their association with the risk of gout: A population-based cohort study. Arthritis Care & Research. https://doi.org/10.1002/acr.70007
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