Gut to Lung: Oral Nanoplastic-Induced Microbial Shifts Provoke Systemic Inflammation and Pulmonary Dysfunction

Abstract

Oral exposure to nanoplastics (NPs) adversely affects mammalian health, yet the mechanisms driving distal pulmonary toxicity remain poorly understood. Specifically, how different NP polymers disrupt the gut–lung–microbiota axis is largely elusive. This study investigated the effects of 12-week oral exposure to three common NPs [polystyrene (PS), polypropylene (PP), and polyethylene (PE)] at environmentally relevant doses (50 μg/d and 500 μg/d) in a murine model, followed by histopathological, microbiomics, and metabolomic analyses to delineate NP-induced alterations in intestinal and pulmonary tissues. Results revealed that all three NPs compromised intestinal barrier integrity through disruption of tight junction proteins, concomitant with marked histopathological alterations and inflammatory infiltration in pulmonary tissues. Among them, PE-NPs provoked the most severe pulmonary inflammation and fibrotic progression. Analysis of the lung microbiome revealed significant shifts in the relative abundance of specific bacterial taxa, where high-dose PE induced the ectopic lung colonization of gut-associated bacteria (e.g., Turicibacter), providing direct evidence of barrier breach and distal dysbiosis. Notably, pulmonary enrichment of Stenotrophomonas and Sphingomonas correlated strongly with inflammatory metabolites (e.g., dehydroabietic acid), suggesting microbiota-driven metabolic reprogramming in the lung. Collectively, our findings establish that oral NP ingestion initiates a pathogenic cascade where gut barrier failure enables cross-organ microbial translocation and metabolic dysregulation, ultimately exacerbating pulmonary fibrosis. This study provides crucial mechanistic insights into the material-specific, distal toxicity of ingested NPs.