Micro- and Nanoplastics and Potential Perturbation of the Microbiota-Gut-Brain Axis

Microplastics (MPs) and nanoplastics (NPs) are pervasive environmental contaminants increasingly investigated for their potential neurotoxicological relevance. This narrative review critically evaluates experimental and emerging human evidence linking plastic exposure to microbiota-gut-brain communication and brain-related vulnerability. MPs and NPs are considered separately because differences in particle size, surface properties, cellular uptake, barrier interactions, and biodistribution constrain toxicological extrapolation across particle classes. Controlled animal studies provide the strongest mechanistic evidence, reporting microbiota compositional and metabolic perturbations, intestinal barrier alterations, systemic inflammatory signaling, neurovascular effects, and neurobehavioral changes under defined exposure conditions. However, these findings are limited by heterogeneous particle characterization, frequent use of pristine model particles, uncertain dose relevance, variable study quality, and incomplete distinction between intrinsic particle effects and toxicity associated with additives or co-contaminants. Evidence for a sequential microbiota-barrier-lipopolysaccharide-neuroinflammation pathway remains incomplete, and individual components should be interpreted as interacting candidate mechanisms rather than an established causal cascade. Human evidence is substantially weaker and is dominated by biomonitoring, post-mortem detection, and early observational associations that cannot establish parenchymal brain exposure or causality for neuropsychiatric or neurodegenerative disease. Progress will require environmentally representative particle libraries, chronic low-dose and route-specific models, spatial validation of brain entry, harmonized contamination-controlled biomonitoring, longitudinal human cohorts, explicit causal frameworks, and validated multi-omic integration. Current evidence therefore supports MPs and NPs as candidate environmental modifiers of neurobiological vulnerability rather than established human neurotoxicants.