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Updated: Aug 18, 2025
Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
Published on: April 30, 2019
Gut microbiota modulates bleomycin-induced acute lung injury response in mice
Young Me Yoon1,2, Cara L Hrusch2, Na Fei3
1Committee on Immunology, University of Chicago, Chicago, IL, USA.
Background:
Airway instillation of bleomycin (BLM) in mice is a widely used, yet challenging, model for acute lung injury (ALI) with high variability in treatment scheme and animal outcomes among investigators. Whether the gut microbiota plays any role in the outcome of BLM-induced lung injury is currently unknown.
Methods:
Intratracheal instillation of BLM into C57BL/6 mice was performed. Fecal microbiomes were analyzed by 16s rRNA amplicon and metagenomic sequencing. Germ-free mice conventionalization and fecal microbiota transfer between SPF mice were performed to determine dominant commensal species that are associated with more severe BLM response. Further, lungs and gut draining lymph nodes of the mice were analyzed by flow cytometry to define immunophenotypes associated with the BLM-sensitive microbiome.
Results:
Mice from two SPF barrier facilities at the University of Chicago exhibited significantly different mortality and weight loss during BLM-induced lung injury. Conventionalizing germ-free mice with SPF microbiota from two different housing facilities recapitulated the respective donors' response to BLM. Fecal microbiota transfer from the facility where the mice had worse mortality into the mice in the facility with more survival rendered recipient mice more susceptible to BLM-induced weight loss in a dominant negative manner. BLM-sensitive phenotype was associated with the presence of Helicobacter and Desulfovibrio in the gut, decreased Th17-neutrophil axis during steady state, and augmented lung neutrophil accumulation during the acute phase of the injury response.
Conclusion:
The composition of gut microbiota has significant impact on BLM-induced wasting and death suggesting a role of the lung-gut axis in lung injury.
Insights
Gut microbiota composition significantly impacts outcomes in bleomycin-induced lung injury (ALI) models. Specific bacteria like Helicobacter and Desulfovibrio are linked to increased susceptibility and mortality in mice.
Area of Science:
- Immunology
- Microbiology
- Pulmonary Medicine
Background:
- Bleomycin (BLM) instillation in mice is a common model for acute lung injury (ALI), but shows high variability.
- The role of gut microbiota in BLM-induced lung injury outcomes is not well understood.
Purpose of the Study:
- To investigate the influence of gut microbiota on the variability of BLM-induced lung injury in mice.
- To identify specific gut microbial species associated with differential responses to BLM.
Main Methods:
- C57BL/6 mice underwent intratracheal BLM instillation.
- Fecal microbiome analysis used 16s rRNA and metagenomic sequencing.
- Germ-free mice conventionalization and fecal microbiota transfer experiments were conducted.
- Lung and gut-draining lymph node immunophenotypes were analyzed via flow cytometry.
Main Results:
- Significant differences in mortality and weight loss were observed between mice from different SPF facilities.
- Conventionalizing germ-free mice with SPF microbiota replicated donor-specific responses to BLM.
- Fecal microbiota transfer from a high-mortality facility increased recipient susceptibility to BLM.
- BLM sensitivity correlated with Helicobacter and Desulfovibrio presence, altered Th17-neutrophil axis, and increased lung neutrophils.
Conclusions:
- Gut microbiota composition significantly affects BLM-induced wasting and mortality.
- These findings suggest a critical role for the lung-gut axis in acute lung injury pathogenesis.
