Microbial Dysbiosis in the Lung and Gut in Response to Inhalable Particulate Matters in Pneumoconiosis Patients and Animals

Pneumoconiosis is a progressive and life-threatening fibrotic lung disorder caused by the prolonged deposition of inhaled particulate matters (PMs); thus far, no cure is available. Emerging evidence has suggested that the resulting disordered respiratory microbiome is caused by disturbed lung architecture and homeostasis responding to inhalable PMs. Lung microbiome dysbiosis also contributes to injury to the lung and distant organs, such as the intestine, through the lung-gut axis. Current studies on the microbiome-disease interplay are still in their infancy, and sufficient understanding of microbial heterogeneity in pathological processes is lacking. Here we investigated the microbiome in the lung and gut of patients with pneumoconiosis in comparison to healthy individuals. Our findings indicated reciprocal causation between lung injuries and microbial dysbiosis under particle exposure; pulmonary <i>Streptococcus</i> and <i>Stenotrophomonas</i>, along with intestinal <i>Ligilactobacillus</i> and <i>Blautia</i>, may represent key microbial communities influencing pneumoconiosis progression. We defined close microbiota crosstalk between the lung and gut, as evidenced by their interaction networks, implying considerable effects on the gut microenvironment through either direct microbial translocation or other mechanisms such as inflammation-driven alterations. Animal experiments further corroborated the findings in humans. Collectively, our results highlight the potential involvement of the lung-gut axis microbial dysbiosis in pneumoconiosis pathogenesis and open a new avenue to develop microbiome-targeted diagnosis and treatment strategies.