Abstract

Environmental pollutants, including heavy metals, persistent organic pollutants (POPs), endocrine-disrupting chemicals (EDCs), particulate matter, and emerging contaminants such as microplastics, are increasingly associated with the development of chronic human diseases. While the toxicological effects of individual pollutant classes are well established, the integrated molecular mechanisms that link chronic exposure to long-term pathological outcomes remain poorly defined. It is a systematic, mechanistic-oriented review that summarizes the results of 214 epidemiological, experimental, and multi-omics studies to form a concise model of biological disturbance caused by contaminants. The information retrieved in PubMed, Scopus, Web of Science, and ScienceDirect was reviewed, considering the pollutant-targeted modification of oxidative stress, inflammatory signaling, mitochondrial dysfunction, genomic instability, and epigenetic reprogramming. The highest oxidative signature was observed with heavy metals, where 84.1% of the studies indicated redox imbalance, and particulate matter stimulated the greatest inflammatory response (88.5%). POPs exhibited strong epigenetic (71.2%) effects, and EDCs had serious impacts on hormonal and gene-regulatory pathways. Quantitative synthesis revealed a 42.6% rise in reactive oxygen species, a 92.6% increase in lipid peroxidation, and a 28–32% reduction in key antioxidant enzymes and ATP production among exposed populations. Mitochondrial membrane potential declined by 27.8%, and epigenetic markers, including DNA methylation profiles and microRNA expression, showed persistent dysregulation with evidence of transgenerational retention. Multi-omics integration revealed a 71% convergence across disrupted pathways, identifying mitochondrial impairment, NF-κB–mediated inflammation, DNA repair inhibition, and epigenetic remodeling as central mechanistic hubs. The integrated model developed through this review provides a comprehensive explanation of how pollutant exposure increases the risk of cardiometabolic, respiratory, neurodegenerative, and metabolic diseases. These findings underscore the need for biomarker-based risk assessment, mixture-toxicity research, and longitudinal multi-omics studies to enhance disease prediction and prevention.