Associations between PM2.5 exposure and COPD and gastrointestinal conditions: Underlying lung-gut metabolic communication

Hui Shi; Tong Hou; Lei Tan; Shanshan Ran; Shengtao Wei; Guzhengyue Zheng; Jingyi Zhang; Zijun Yang; Jiyang Zhang; Wenjun Fan; Sanduo Li; Fei Tian; Zilong Zhang; Hualiang Lin

doi:10.59717/j.xinn-med.2025.100175

The Innovation Medicine > 2025 Vol. 3 > No. 4 > 100175

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Associations between PM_2.5 exposure and COPD and gastrointestinal conditions: Underlying lung-gut metabolic communication

1.
Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
2.
School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China
3.
Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
4.
These authors contributed equally

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Corresponding author: linhualiang@mail.sysu.edu.cn
Received Date: February 28, 2025

Accepted Date: November 17, 2025

Published Online: November 19, 2025

The Innovation Medicine 3(4), https://doi.org/10.59717/j.xinn-med.2025.100175 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Exposure to PM_2.5 increases the risk of disease transition between COPD and gastrointestinal (GI) diseases.
  
  PM_2.5 alters the gut microbiome, affecting lung and gut metabolites and inflammation in both regions.
  
  Imbalance metabolic communication between the lung and gut under PM_2.5 exposure.
  
  Tryptophan and glycerophospholipid metabolism changes are key to lung-gut communication upon PM_2.5 exposure.

ABSTRACT

ABSTRACT

BackgroundWhile the individual effects of PM_2.5 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 PM_2.5 exposure and the risk of chronic obstructive pulmonary disease (COPD) and GI diseases and to explore lung‒gut metabolic communication.
MethodsData from the UK Biobank were analysed. The PM_2.5-related metabolic signature was evaluated via elastic net regression analysis. A multistate model was used to assess the dynamic impact of PM_2.5 on COPD and four GI diseases. Male C57BL/6N mice were exposed to PM_2.5 or filtered air for 8 weeks. Underlying metabolic mechanisms were elucidated through multiomics analyses.
ResultsOur cohort analysis showed that PM_2.5 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, PM_2.5-related metabolomic profiles affect COPD and IBD transition. Exposure to PM_2.5 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.
ConclusionA significant dynamic association was found between PM_2.5 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 PM_2.5 exposure, as identified in animal experiments.

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Shi H., Hou T., Tan L., et al. (2025). Associations between PM2.5 exposure and COPD and gastrointestinal conditions: Underlying lung-gut metabolic communication. The Innovation Medicine 3:100175. https://doi.org/10.59717/j.xinn-med.2025.100175

Shi H., Hou T., Tan L., et al. (2025). Associations between PM_2.5 exposure and COPD and gastrointestinal conditions: Underlying lung-gut metabolic communication. The Innovation Medicine 3:100175. https://doi.org/10.59717/j.xinn-med.2025.100175

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Associations between PM_2.5 exposure and COPD and gastrointestinal conditions: Underlying lung-gut metabolic communication

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