What question did this study set out to answer?

The research aims to understand how different exposures, like multi-walled carbon nanotubes and bleomycin, affect lung microbiome and contribute to pulmonary fibrosis.

April 8, 2026Open Access

Lung Microbiome Dysbiosis in Pulmonary Fibrosis Induced by Multi-Walled Carbon Nanotubes and Bleomycin in Rats

Key Points

The research aims to understand how different exposures, like multi-walled carbon nanotubes and bleomycin, affect lung microbiome and contribute to pulmonary fibrosis.
Female Wistar rats were exposed to vehicle, MWCNTs, or bleomycin through intratracheal instillation.
Lung fibrosis and inflammation were assessed using histopathology and bronchoalveolar lavage fluid analysis.
Lung microbial communities were characterized through 16S rRNA gene sequencing.
Seventeen lung samples were analyzed post-exposure, including controls and treatment groups.
Both MWCNTs and bleomycin induced pulmonary fibrosis with different pathological effects.
Bleomycin exposure increased microbial richness and shifted community structure significantly.
Pseudogracilibacillus was more abundant in the bleomycin group, while Facklamia and Corynebacterium were richer in the MWCNT group.
Proteobacteria levels were inversely related to TGF-β and MCP-1 in BALF, indicating a potential biomarker link.

Abstract

Background and objectives: Occupational and environmental inhalation exposures, including high-aspect-ratio carbon nanotubes, can trigger pulmonary fibrosis (PF). The relationship between exposure-specific fibrogenic pathways (granulomatous inflammation versus diffuse epithelial injury) and lung microbiome dysbiosis remains incompletely understood. We therefore compared lung microbiome alterations in rat PF models induced by multi-walled carbon nanotubes (MWCNTs) and bleomycin. Materials and Methods: Female Wistar rats received a single intratracheal instillation of vehicle, MWCNTs (750 μg/rat), or bleomycin (1 mg/rat). At day 28, fibrosis and inflammation were evaluated by histopathology and bronchoalveolar lavage fluid (BALF) profiling. Lung microbial communities were characterized by 16S rRNA gene sequencing (V3–V4). Seventeen lung samples passed stringent quality control and were analyzed (control n = 5; bleomycin n = 7; MWCNT n = 5). Results: Both agents induced PF with increased profibrotic signaling, but with distinct pathological signatures: MWCNTs produced localized granulomatous lesions and a robust neutrophilic response (25% of BALF cells), whereas bleomycin caused diffuse interstitial remodeling. Bleomycin increased microbial richness (alpha diversity; p < 0.05) and significantly shifted community structure (beta diversity; p < 0.05), while MWCNT exposure showed comparatively limited changes in global diversity. The relative abundance of Pseudogracilibacillus (including P. marinus) was higher in the bleomycin group than in controls, whereas Facklamia tabacinasalis and Corynebacterium maris were more abundant in the MWCNT group. Across samples, Proteobacteria abundance was inversely correlated with BALF TGF-β, MCP-1, and neutrophil proportion. At the species level, Pseudogracilibacillus marinus was positively correlated with BALF TGF-β, while Facklamia tabacinasalis and Corynebacterium maris were positively correlated with MCP-1, CINC-3, and neutrophil proportion (Spearman; p < 0.05). Conclusions: Mechanistically distinct fibrogenic exposures generate exposure-linked lung microbiome signatures that track with host inflammatory and profibrotic responses. These signatures may support biomarker development for environmentally and occupationally relevant PF and motivate longitudinal and functional studies to clarify causality.

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