MPTmouse

Microplastics (MPs) exposure has emerged as a global environmental crisis with potential threats to human health, particularly concerning the development of diseases. However, under conditions that simulate real-world human exposure, significant challenges remain in elucidating the molecular mechanisms underlying MPs-induced effects and their relevance to disease pathogenesis. In this study, we developed MPTmouse, a comprehensive and quantitative map of the mouse transcriptomic regulation by MPs exposure. We observed widespread remodeling of the transcriptome and molecular interaction networks driven by MPs across multiple tissues, even in the absence of overt tissue damage. When MPs were combined with additional physiological stressors such as aging, we identified pronounced alterations in MPs-associated regulatory pathways. Furthermore, MPs exposure can induce a state of pathological vulnerability, characterized by perturbation of specific key genes, that predisposing individuals to disease progression when interacting with other factors such as metabolic disorders, infections, and aging. Using an artificial intelligence approach, we dissected the molecular basis linking MP-perturbed gene networks to major human diseases. Collectively, we present MPTmouse together with a disease association compendium as a framework for understanding the regulatory impact of MPs on physiology and aging.