Metabolomics‐Based Insights Into the Toxicological Effects and Mechanisms of Microplastics: A Comprehensive Review

Microplastics (MPs), a pervasive environmental pollutant, present a significant and growing threat to human health. Metabolomics has emerged as a powerful tool for deciphering pollutant toxicity by sensitively detecting metabolic perturbations. This review outlines metabolomic methodologies and their application in environmental toxicology. Meanwhile, evidence of the multisystem toxic effects of MPs revealed by metabolomics is synthesized, and progress in integrating metabolomic data with multiomics to elucidate underlying mechanisms is summarized. Results indicate that MPs induce systemic toxicity through organ-specific metabolic disruptions. In the intestinal tract, MPs compromise barrier integrity, induce amino acid and lipid metabolic reprogramming, and cause microbial dysbiosis, impacting distal organs via the gut-organ axes. Upon entering the nervous system, they disrupt neurotransmitter metabolism and impair cognitive function. Concurrently, MPs impair reproductive function by altering testicular phospholipid metabolism, reducing sperm quality, and disrupting placental lysine and glucose homeostasis, restricting fetal growth. Furthermore, MPs inhibit central energy metabolism pathways, including glycolysis and the tricarboxylic acid cycle across diverse species, resulting in impaired growth and development. Future research should leverage spatial metabolomics, causal validation techniques, and advanced computational algorithms to systematically map MP-induced metabolic disruptions, establish definitive mechanistic links, and reconstruct toxicity networks. Our study provides scientific basis for further clarifying the MP toxicity and identifying molecular targets of metabolic reprogramming to develop interventions that mitigate the health risks of MPs.