Molecular insights into physiological impact of micro- and nano-plastics on the digestive system and gut-brain axis

Microplastics (MPs) and Nanoplastics (NPs) represent an alarming and persistent threat to global human health, owing to their resilience and ubiquity in the environment. Ingestion via contaminated food and water is the primary exposure route, resulting in the accumulation of MNPs in key organs such as the gastrointestinal tract (GI), liver, and pancreas, highlighting the urgent need to understand their potential cumulative and systemic effects. This review critically evaluates recent molecular-level insights into the physiological impacts of MNPs, with particular emphasis on the GI system and the intricate gut-brain axis. MNPs induce cellular toxicity through oxidative stress (OS) and mitochondrial dysfunction, which activate inflammatory and apoptotic pathways. Accumulation in the GI tract causes gut microbiota dysbiosis and a compromised intestinal barrier, and translocates systemically to the liver and pancreas, leading to hepatotoxicity, insulin resistance, and chronic inflammation. Crucially, the disruption of the gut barrier facilitates MNPs access to the central nervous system (CNS) via the gut-brain axis, leading to a breach of the Blood-Brain Barrier. CNS-accumulated MNPs induce neuroinflammation and neurotoxicity, accelerating neurodegenerative disorders such as Parkinson's, Alzheimer's, and multiple sclerosis. This review elucidates the complex mechanisms and highlights significant gaps in understanding MNPs risks, which are currently limited by the use of short-term animal and in vitro models, as well as a lack of precise human data. Future research should prioritize the development of standardized quantification techniques and advanced tracking methods to accurately assess the biodistribution, metabolism, and long-term health effects of MNPs. This approach will facilitate the development of targeted therapeutic interventions and preventive measures.