Micro- and Nanoplastics as Disruptors of Digestive and Hepatopancreatic Homeostasis: Insights into the Plastic-Gut-Liver Axis.

Micro- and nanoplastics (MPs/NPs) have emerged as pervasive environmental contaminants with increasing implications for human health, particularly within the digestive system. This review critically examines the role of MPs/NPs as disruptors of gastrointestinal and liver homeostasis through the lens of the plastic-gut-liver axis. We synthesize current evidence on primary exposure routes-including ingestion, inhalation, dermal contact, and transplacental transfer-and highlight their intestinal uptake, systemic dissemination, and tissue accumulation. Mechanistically, MPs/NPs compromise intestinal barrier integrity, promote oxidative stress, and induce microbiota dysbiosis, facilitating the translocation of microbial-derived signals to the liver via the portal circulation. This process triggers inflammatory signaling cascades, metabolic reprogramming, and immune dysregulation, contributing to hepatic steatosis, insulin resistance, and potential carcinogenic processes. Emerging evidence also implicates pancreatic dysfunction and β-cell stress within a broader gut-liver axis context. We further discuss the systemic propagation of MPs/NPs-induced dysbiosis along multi-organ axes, including gut-lung and gut-brain interactions. Despite robust preclinical data, human evidence remains limited due to methodological heterogeneity and the lack of standardized biomarkers. This review underscores critical knowledge gaps and emphasizes the need for integrative, translational approaches to clarify long-term health risks and inform regulatory strategies within the environmental exposome framework.