February 6, 2023

Gut microbiota and lung fibrosis

Microorganisms residing in the gut influence the severity of lung fibrosis in mouse models, suggesting that modifying the gut microbiota may offer therapeutic benefit for patients.

by Leigh MacMillan

Growing evidence supports a gut-lung axis: a connection between the gut, including its microorganisms (microbiota), and lung disease outcomes. 

Wonder Drake, MD, and colleagues explored the influence of the gut microbiota on lung fibrosis using mice housed in conditions of increasing microbe exposure: germ-free, biosafety level 1 (ABSL-1), and biosafety level 2 (ABSL-2). Using a lung injury model, they found that germ-free mice were protected from lung fibrosis, and ABSL-1 and ABSL-2 mice developed mild and severe lung fibrosis, respectively. 

Metagenomic analysis showed that ABSL-1 gut microbiota had greater diversity and increased prevalence of bacterial species associated with anti-inflammatory activity compared to ABSL-2 gut microbiota. Fecal transplantation of ABSL-2 stool into germ-free mice before lung injury resulted in more severe lung fibrosis compared to transplantation of ABSL-1 stool. 

The findings, reported in Communications Biology, support a functional role of gut microbiota in modulating lung fibrosis severity and suggest that enhancing gut microbial diversity may offer therapeutic benefit for patients with interstitial lung disease.

Co-authors include Ozioma Chioma, PhD, Elizabeth Mallott, PhD, Austin Chapman, MS, Joseph Van Amburg, MS, Hongmei Wu, Binal Shah-Gandhi, PhD, Nandita Dey, Marina Kirkland, PhD, M. Blanca Piazuelo, MD, Joyce Johnson, MD, Gordon Bernard, MD, Sobha Bodduluri, Steven Davison, DVM, Bodduluri Haribabu, PhD, and Seth Bordenstein, PhD. 

The research was supported by the National Institutes of Health (grants HL127301, HL149129), Ellen Dreiling Research Fund Endowment, and Vanderbilt Microbiome Initiative.