Human exposure to microplastics and insights into microplastics as obesogens and other metabolic disorders

The proliferation of plastic pollution has driven the pervasive environmental contamination by microplastics (MPs, <5 mm) and nanoplastics (NPs, <1 μm), leading to chronic human exposure through ingestion, inhalation, and transplacental transfer. This review critically examines the current state of knowledge regarding internal MPs exposure and its profound impact on human health. We synthesize evidence demonstrating that MPs act not only as physical contaminants but also as potent vectors for chemical additives—such as phthalates, bisphenols, and organotins—which acts as endocrine-disrupting chemicals (EDCs) and environmental obesogens. Mechanistically, MPs and their leachates are shown to dysregulate molecular signaling activation, and drive systemic metabolic dysfunction. These include the induction of chronic, low-grade inflammation (linked to metabolic endotoxemia and insulin resistance), mitochondrial dysfunction and oxidative stress, and the alteration of the gut microbiome composition. Furthermore, we highlighted preclinical evidence linking MPs exposure to the pathogenesis of neurodegenerative conditions, including Alzheimer's disease (AD) and Parkinson's disease (PD), mediated by blood–brain barrier disruption, neuroinflammation, and the accelerated aggregation of pathological proteins. Despite clear mechanistic insights, the precise causal relationship in human populations is obscured by a lack of standardized analytical methods and comprehensive epidemiological data. We conclude by advocating for urgent, interdisciplinary strategies—integrating high-resolution biomonitoring, advanced in vitro models, regulatory policy, and public health initiatives—to mitigate exposure and safeguard metabolic and neurological health globally.