Polylactic acid microplastics before and after aging induced neurotoxicity in zebrafish by disrupting the microbiota-gut-brain axis

Polylactic acid (PLA) is a biodegradable alternative to traditional plastics due to its excellent biocompatibility. However, PLA is challenging to fully degrade and can easily become microplastics (MPs) in surface water, a process accompanied by aging. This study found that aged PLA (APLA) MPs exhibited increased surface roughness, decreased surface potential, and more oxygen-containing functional groups compared to PLA. Acute exposure to PLA/APLA in zebrafish larvae resulted in sluggish behavior and inhibited neuronal development. Chronic exposure to PLA/APLA in adult zebrafish led to reduced exploratory behavior, poor memory, increased aggression, and neuron loss. Overall, PLA/APLA induced dose-dependent neurotoxicity, with APLA exhibiting greater toxicity than PLA, potentially due to its higher rate of uptake. Additionally, exposure to PLA/APLA led to thinning of the intestinal wall, shortening of villi, and suppression of intestinal neurotransmitter levels, accompanied by alterations in microbial abundance and gut dysbiosis. Meanwhile, supplementation with bile acid, considered as the key regulator in the gut-brain axis, significantly mitigated the neurotoxicity induced by PLA/APLA. These findings confirm that PLA/APLA MPs indeed elicit neurotoxicity via the gut-brain axis and provide scientific evidence for targeted environmental interventions to minimize the adverse ecological impacts of biodegradable MPs.