Coal Dust Nanoparticles Induce Colitis-Like Lesions in Rats via Gut Microbiota Dysbiosis and P53/SCO2/SLC7A11-Mediated Epithelial Ferroptosis.

Abstract

Purpose: Advanced mining technologies have increased the generation and exposure risk of coal dust nanoparticles (CD-NPs). While CD-NPs are known to cause lung damage, their effects on intestinal tissues following respiratory exposure remain unclear. Here, we investigated the damaging effects of CD-NPs on colonic tissues and the underlying mechanisms.

Methods: Rats were exposed to CD-NPs for 3, 6, and 9 weeks (n = 6 per group). Assessments included intestinal pathology, inflammatory status, barrier integrity, gut microbiota (16S rRNA sequencing), colonic transcriptomics (RNA-Seq), and cellular functional validation of ferroptosis pathways.

Results:  : CD-NPs exposure caused significant colonic damage, elevated interleukin-6 / interleukin-17a levels, and reduced expression of tight junction proteins (Zonula occludens-1, Occludin, Claudin-1; all P < 0.05). The gut microbiota exhibited decreased alpha diversity, distinct beta separation, enriched pro-inflammatory taxa, and depleted anti-inflammatory commensals. Transcriptomics revealed downregulated oxidative phosphorylation and enriched ferroptosis (both P < 0.01). Functional experiments confirmed ferroptosis characteristics: reduced glutathione peroxidase 4, increased long-chain acyl-CoA synthetase 4, oxidative stress, mitochondrial dysfunction, Fe²⁺ accumulation, and activation of the tumor protein 53 (P53)/synthesis of cytochrome C oxidase 2 (SCO2)/solute carrier family 7 member 11 (SLC7A11) pathway.

Conclusion: Respiratory exposure to CD-NPs induces colitis-like lesions via gut microbiota dysbiosis and P53/SCO2/SLC7A11-mediated epithelial ferroptosis, impairing the intestinal barrier. These findings provide new insights into the health risks associated with coal dust exposure.