Systemic toxicity of biodegradable polyglycolic acid microplastics on the gut-liver-brain axis in zebrafish

Polyglycolic acid (PGA), a novel type of hazardous biodegradable plastic, is gradually being widely used in the biomedical and food packaging industries. However, the long-term ecological effects of PGA degradation to microplastics (MPs) in aquatic organisms remain unknown. The gut-liver-brain axis regulates the exchange of information between the gut, liver, and brain, and is a key target for tissue damage caused by pollutants. Adult zebrafish were exposed to 1 or 100 mg/L PGA MP suspension for 28 d. PGA affects the intestinal vascular barrier through gene expression downstream of the Wnt/β-catenin pathway, increasing intestinal permeability and disrupting the environment of intestinal microbial diversity. This, in turn, promoted the accumulation of lipopolysaccharide (LPS). Disturbance of the intestinal microbiota balance and its metabolites are transferred to the liver and brain through the gut-liver-brain axis, causing disorders in hepatic lipid metabolism and synthesis. Behavioural experiments showed that long-term exposure to PGA MP caused anxiety-like behaviour and cognitive impairment, which may be related to the disruption of the gut-liver-brain axis, thus inducing inflammation and disrupting the normal functioning of the body. In summary, this study evaluated the safety of the new degradable plastic, PGA, but its ecological risks still require attention. • PGA caused anxiety-like-behaviour and cognitive impairment in zebrafish through novel tank experiments and colour preference experiments. It also impairs the brain's 5-HT system by Elisa experiments. • The present study demonstrates that PGA influences intestinal permeability through the regulation of gene expression downstream of the Wnt/β-catenin pathway. This was evidenced by the use of qpcr, Elisa and tissue section analysis. • PGA mediates gut microbiota disruption through 16S rRNA sequencing analysis. It also affects liver injury and neurobehavioral disorders through histopathological observations and qpcr, Elisa experiments. • Disturbance of the gut-liver-brain axis as a manifestation of toxicity from chronic PGA exposure through behavioural and biochemical experiments.