Microplastics accumulate in human bile and drive cholangiocyte senescence

Microplastics are ubiquitous environmental pollutants that increasingly infiltrate human organs and tissues through multiple exposure pathways. While acute toxicological impacts have been documented, the metabolic fate of these polymers within the enterohepatic circulation remains poorly understood. Bile serves as a critical excretory fluid, and disruptions in its balance can lead to biliary tract diseases such as gallstones. However, the long-term accumulation patterns and chronic toxic effects of microplastics within the human biliary system are largely unknown. Here we show the universal presence of microplastics in human bile. Using a multimodal analytical approach, we identified six polymer types, predominantly polyethylene terephthalate and polyethylene, occurring primarily as 20–50 μm particles. We demonstrate that chronic, low-dose exposure to these microplastics induces mitochondrial dysfunction-associated senescence in cholangiocytes. Notably, targeted antioxidant intervention with melatonin effectively preserves mitochondrial function and mitigates this microplastic-induced cytotoxicity. These findings reveal the biliary system as a major reservoir for microplastic accumulation and excretion. Furthermore, they provide a mechanistic foundation for assessing the health risks of plastic pollution and developing therapeutic interventions for environmentally driven biliary disorders. • Microplastics are universally present in human bile samples. • Biliary microplastic concentrations are significantly higher in patients with gallstones. • Chronic low-dose microplastic exposure induces mitochondrial senescence in cholangiocytes. • Melatonin effectively mitigates microplastic-induced cellular toxicity and senescence.