Axis-based propagation of nanoplastic toxicity: organ–organ crosstalk and systemic pathophysiological outcomes

Nanoplastics (NPs) are emerging as environmental pollutants with the capacity to penetrate biological barriers, distribute systemically, and cause toxicity to multiple organs. Although early studies have primarily focused on localized organ damage, growing evidence suggests that NPs exert broader biological effects by disrupting interorgan communication through established physiological axes. In this review, we examined NP-induced toxicity through seven critical organ-organ pathways, including the gut-liver, gut-brain, gut-endocrine, liver-kidney, hypothalamus-pituitary-gonadal (HPG), hypothalamus-pituitary-adrenal (HPA), and placenta-fetus. NPs initiate damage at primary exposure sites, such as the intestinal epithelium or hypothalamic neurons, which propagates to secondary organs through hormonal, immunologic, and metabolic signaling. Shared histopathological features, including epithelial or parenchymal degeneration, inflammatory infiltration, and fibrotic remodeling, are consistently observed across axis-linked tissues. Moreover, bidirectional feedback mechanisms within these axes amplify NP-induced dysfunction and promote system-wide pathology. The ability of NPs to cross the placental barrier, accumulate in fetal tissues, and disrupt organ development is of particular concern and suggesting a potential for transgenerational toxicity. Overall, this axis-based framework highlights NPs as systemic toxicants that compromise the integrity of interconnected biological systems. In addition to single-organ perspectives, this review proposes an integrative model for understanding the complex and often indirect effects of chronic NP exposure on organismal health.