Abstract
Background
While the individual effects of PM2.5 on the respiratory and gastrointestinal (GI) systems are known, its combined impact on these organs and the underlying mechanisms involved remain unclear. We aimed to investigate the associations between PM2.5 exposure and the risk of chronic obstructive pulmonary disease (COPD) and GI diseases and to explore lung-gut metabolic communication.
Methods
Data from the UK Biobank were analysed. The PM2.5-related metabolic signature was evaluated via elastic net regression analysis. A multistate model was used to assess the dynamic impact of PM2.5 on COPD and four GI diseases. Male C57BL/6N mice were exposed to PM2.5 or filtered air for 8 weeks. Underlying metabolic mechanisms were elucidated through multiomics analyses.
Results
Our cohort analysis showed that PM2.5 exposure affects the transition from COPD to inflammatory bowel disease (IBD) [HR (95% CI): 1.23 (1.09, 1.49)] and from IBD to COPD [HR (95% CI): 1.09 (1.02, 1.47)]. Similarly, PM2.5-related metabolomic profiles affect COPD and IBD transition. Exposure to PM2.5 induced metabolic alterations in lung and gut tissues. Multiomics analysis revealed that tryptophan and glycerophospholipid metabolites were significantly associated with inflammatory markers and the key gut microbiome. Mediation analysis showed that key metabolites mediate the associations between the gut microbiome and inflammatory markers.
Conclusion
A significant dynamic association was found between PM2.5 exposure and the risk of COPD and GI diseases. This association may be attributed to the crucial role of tryptophan and glycerophospholipid metabolism in mediating lung and gut communication under PM2.5 exposure, as identified in animal experiments.