New Research links Gut bacteria and Inflammatory Proteins to Idiopathic Pulmonary Fibrosis
Groundbreaking research suggests a connection between the gut microbiome, specific inflammatory proteins, and the development of idiopathic pulmonary fibrosis (IPF), a chronic and ultimately fatal lung disease. A two-step, two-sample Mendelian randomization study published in Clinical Respiratory Journal in 2025 identified a notable association between Actinomyces bacteria and circulating levels of CCL11, an inflammatory protein, with an increased risk of IPF. This revelation opens new avenues for potential therapeutic interventions targeting the gut microbiome to prevent or slow the progression of this devastating condition.
IPF affects thousands worldwide, causing progressive scarring of the lungs and leading to breathing difficulties and reduced quality of life. Currently,treatment options are limited,and lung transplantation remains the only definitive cure. This study, utilizing data from large-scale genetic analyses, offers a potential paradigm shift in understanding IPF’s origins and progression. Researchers hope that by modulating the gut microbiome and its influence on inflammatory pathways, they can develop novel strategies to manage and potentially halt the disease.
The study, led by Zhu H, Chen C, Guo H, Zhang B, and Hu Q, employed Mendelian randomization to assess the causal relationship between gut microbiota and IPF, mediated by circulating inflammatory proteins.Researchers found that inhibiting CCL11 release from T helper 2 cells “could control the transition from an acute inflammatory response to chronic fibrosis,” according to a related study published in arch Toxicol in 2016.
Though, the investigators acknowledge limitations in their research. The datasets primarily represented European populations, potentially limiting the generalizability of the findings to other ethnicities. Additionally, the study focused on 211 bacteria and 91 circulating inflammatory proteins, and analyzed approximately 14,000 bacterial samples and cases, which could introduce bias. The authors also noted that other unstudied mediators may play a role in IPF development.
Previous research has highlighted the importance of gut health in respiratory diseases. A 2021 study in Cureus found an association between intestinal microbial dysbiosis and chronic obstructive pulmonary disease, while a 2024 study in Acute Med Surg linked gut microbiota dysbiosis to severe COVID-19. Further research is planned to explore how these findings regarding Actinomyces and CCL11 can be translated into clinical applications.
References
- Zhu H, Chen C, Guo H, Zhang B, Hu Q. The role of gut microbiota on idiopathic pulmonary fibrosis mediated by circulating inflammatory proteins: A two-step, two-sample Mendelian randomization study. Clin Respir J. 2025;19(9):e70120. doi:10.1111/crj.70120
- ananya FN, Ahammed MR, Fahem MM, et al. Association of intestinal microbial dysbiosis with chronic obstructive pulmonary disease. Cureus. 2021; 13 (11): E19343.doi: 10.7759/Cureus.19343
- Shimizu K, hirata H, Tokuhira N, et al. dysbiosis of gut microbiota in patients with severe COVID-19. Acute Med Surg. 2024; 11 (1): E923. doi: 10.1002/AMS2.923
- Dong J, Ma Q. In vivo activation of a T helper 2-driven innate immune response in lung fibrosis induced by multi-walled carbon nanotubes. Arch Toxicol. 2016; 90 (9): 2231-2248. doi: 10.1007/s00204-016-1711-1
