Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential

dysbiosisepithelial-mesenchymal transitionfecal microbiota transplantationgut-lung axisidiopathic pulmonary fibrosis

Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential

Why this matters for your gut health

Pulmonary fibrosis (PF) is a progressive, irreversible, and life-threatening lung disease with limited treatment options. This review reframes PF not as a purely local lung disease but as a condition deeply influenced by the gut-lung microbial axis. Understanding this bidirectional relationship opens new diagnostic (microbial biomarkers) and therapeutic (microbiota-targeted) avenues for a disease that currently has few effective interventions.

Summary

The review synthesizes clinical and preclinical evidence showing that PF patients (idiopathic pulmonary fibrosis, silicosis, coal workers’ pneumoconiosis) exhibit reduced lung microbial diversity and altered gut microbiota composition. It identifies five core mechanisms linking microbiota dysbiosis to fibrosis progression: immune dysregulation, gut-lung barrier dysfunction, Type 2 epithelial-mesenchymal transition (EMT), autophagy modulation, and corisin-peptide-mediated alveolar epithelial apoptosis. Key microbial metabolites (tryptophan derivatives, SCFAs, LPS, bile acids) exert synergistic/antagonistic bidirectional effects on fibrosis. The paper also reviews microbiota-targeted therapies—probiotics/prebiotics, fecal microbiota transplantation (FMT), dietary/lifestyle changes, and antibiotics—and outlines challenges (unclear causality, lack of standardized protocols) plus future research directions.

Key findings

IPF patients show significantly reduced lung microbial (Shannon/Simpson) diversity, correlating with disease severity and mortality; Streptococcus enrichment is linked to IPF deterioration.
Silicosis/CWP patients show gut dysbiosis: ↑Proteobacteria (+47.2%), ↑Verrucomicrobia (+32.8%), ↓Firmicutes (−38.5%).
Animal models (bleomycin- and silica-induced) show consistent microbiota shifts — e.g., protective AlloPrevotella drops to 1/7.3 of normal, pathogenic Parasmallomonas rises to 9.2x normal.
SCFAs (via GPR43/GPR109A) balance Treg/Th17 cells; tryptophan metabolites act via AhR pathway to modulate immunity.
LPS drives fibrosis via TLR4/NF-κB signaling; antibiotics reducing LPS can alleviate fibrosis.
The bacterial peptide “corisin” induces alveolar epithelial cell apoptosis and is elevated in acute PF exacerbations.
Probiotics (e.g., Bifidobacterium longum BB536), FMT, and dietary fiber show experimental anti-fibrotic efficacy, though clinical translation remains unstandardized.

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Citation

Yang J, Wang J, Li J and Yang S (2025). Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential. Front. Microbiol. 16:1711299. doi: 10.3389/fmicb.2025.1711299