Biomicroplastics and Antibiotics: A Toxic Cocktail for Fatty Liver Disease in Marine Medaka

The increasing production and use of bioplastics contribute to the accumulation of bioplastic debris in marine environments. The impact of such debris, particularly when combined with co-occurring pollutants like antibiotics, on marine life remains largely unexplored. In this study, we demonstrate that coexposure to aged polylactic acid (PLA) biomicroplastics and the antibiotic sulfamethazine (SMZ) induces overweight (an increase of 20.9-26.2%) and fatty liver-like disease in juvenile marine medaka (<i>Oryzias melastigma</i>). We investigated the underlying mechanism involving the orchestration of physiological processes between the host and its gut microbiota. We found that SMZ acted as a precondition or driver, while PLA acted as an environmental selective pressure, directionally shaping the gut microbiota communities. This altered microbiota demonstrated an increased ability to break down PLA into lactic acid, activating intestinal gluconeogenesis and consequently generating glucose. Excessive glucose shifted the hepatic glucose-fat balance toward fat accumulation, resulting in triglyceride and lipid droplet accumulation and overweight in the fish. Given the prevalent co-occurrence and interaction of PLA and antibiotics in the real-world environment, the combined ecological risk posed by these pollutants requires further investigation.