Microplastics and nano-plastics as emerging gut-brain axis disruptors: mechanistic insights, health implications, and...

Plastics are synthetic polymers widely used for their versatility, longer shelf life, and low cost. However, the non-biodegradable nature of conventional plastics has led to accumulation of microplastics (MPs; <5mm) and nanoplastics (NPs; <100 nm) in aquatic, terrestrial, and atmospheric environments. MNPs are composed of polyethene, polypropylene, polystyrene, polyvinyl chloride, and polyethene terephthalate. Human exposure to micro and nanoplastics occurs mainly through ingestion, inhalation, and rarely through dermal contact. The gastrointestinal tract is the potential accumulation site for such particles, which leads to microbial dysbiosis, disturbs intestinal barrier integrity and induces oxidative stress and inflammation. These disruptions lead to diseases related to the gastrointestinal tract, chronic systemic inflammation and affect the gut-brain axis with neuroinflammatory consequences. This review highlights gut dysbiosis and intestinal barrier disruption as a crucial gateway mediating the systemic effects of MNPs. On exposure to MNPs, gut microbial composition is altered by reducing beneficial short-chain fatty acid-producing bacteria such as Faecalibacterium, Roseburia, and Bifidobacterium, while stimulating the growth of opportunistic pathogens such as Desulfovibrio spp. Subsequent reductions in short-chain fatty acid generation induce lipopolysaccharide release and downregulation of tight junction proteins that compromise intestinal barrier integrity and expedite the translocation of MNPs, microbial products, and pro-inflammatory determinants into systemic circulation. MNPs then cross the blood-brain barrier by receptor-mediated routes, paracellular diffusion, or transcytosis, which is exacerbated by inflammation and oxidative stress. Excessive ROS further cause mitochondrial dysfunction, neuroinflammation, microglial activation, neurotransmitter imbalance, and pathological protein aggregation. This is a narrative review, focusing on integrating current evidence on the role of MNPs in disturbing the gut-brain axis through gut dysbiosis, intestinal barrier dysfunction, increased oxidative stress, inflammation, and altered neurochemical signaling. It further highlights the consequences of these changes in systemic health, identifies key knowledge gaps, and outlines future research priorities to better understand and mitigate the health risks.