Micro/nanoplastics and lithium iron phosphate at environmentally relevant dose triggers hepatic fibrosis: Unseen risks of global renewable energy.

The rapid expansion of the global renewable energy industry has led to increasing environmental release of LiFePO₄ (LFP) and polyvinyl chloride-derived micro/nanoplastics (PVC), yet their combined impacts remain largely unexplored. Here, we demonstrate that chronic co-exposure to environmentally relevant levels of PVC and LFP exerts synergistic hepatotoxicity through a gut-liver axis. Multi-omics integration reveals that co-exposure disrupts intestinal microbial homeostasis, depletes short-chain fatty acids, barrier integrity, and elevates plasma lipopolysaccharide (LPS) and pro-inflammatory cytokines. This gut barrier disruption permits portal translocation of LPS, PVC, and iron, initiating a hepatic inflammatory cascade. Concurrently, PVC and iron enrichment in both the intestine and liver, and lithium depletion in the liver under co-exposure exacerbate oxidative stress. Transcriptomic profiling identifies activation of the p38-cPLA₂-arachidonic acid axis and TGF-β/α-SMA signaling, linking metabolic inflammation to extracellular matrix remodeling and fibrosis. In vitro assays further confirm that co-exposures induce synergistic cytotoxicity and upregulate fibrogenic proteins. Collectively, these findings provide the first mechanistic evidence that co-exposure enhances hepatic fibrosis. This study not only underscores the overlooked health risks posed by composite pollution from renewable energy systems but also highlights the urgent need for sustainable material management and toxicity-informed design in the clean energy transition.