Ingested microplastics and the gut-brain axis: A systematic review of mechanistic pathways and neurobiological impacts in human and preclinical models

Miroplastic (MP) pollution which affects both humans and animals, has emerged as a global health concern. Evidence from in vivo rodent studies, in vitro human cell models, and multi-omics analyses indicates that ingested and inhaled MPs can accumulate in the gastrointestinal tract, cross epithelial barriers, and alter host-microbe interactions. Nanoplastics (NPs, <1 μm), owing to their small size and high surface-area-to-volume ratio, may exhibit greater cellular uptake, tissue translocation, and neurotoxic potential than larger MPs. These processes contribute to systemic effects, including immune activation, oxidative stress, and metabolic dysregulation. Recent studies suggest that MPs influence gut-brain communication, with changes in microbiota composition, neurotransmitter metabolism, and neuroinflammatory signaling linked to cognitive and behavioral deficits in animal models. Promising interventional strategies-including fecal microbiota transplantation (FMT), probiotic supplementation (e.g., Lactobacillus plantarum), and bile acid therapy-have shown efficacy in mitigating MP/NP-induced neurotoxicity in preclinical models. Particle size, surface chemistry, and eco-corona formation modulate these effects, highlighting the importance of physicochemical heterogeneity. Despite progress, translating findings from animals to humans remains challenging, and standardized exposure models are lacking.