Nanoplastics induced health risk: Insights into intestinal barrier homeostasis and potential remediation strategy by dietary intervention.

Aged nanoplastics (aged-NPs) have unique characteristics endowed by environmental actions, such as rough surface, high oxygen content. Although studies have highlighted the potential hazards of aged-NPs, limited research has provided strategies for aged-NPs pollution remediation. The dietary intervention of quercetin is a novel insight to address the health risks of aged-NPs. This study explored the impact of aged-NPs on intestinal barrier homeostasis at the environmentally relevant dose and investigated the alleviating effects of quercetin on aged-NPs toxicity through transcriptomics and molecular biology analysis. It indicated that aged-NPs induced intestinal barrier dysfunction, which was characterized by higher permeability, increased inflammation, and loss of epithelial integrity, while quercetin restored it. Aged-NPs disrupted redox homeostasis, upregulated inflammatory genes controlled by AP-1, and led to Bax-dependent mitochondrial apoptosis. Quercetin intervention effectively mitigated inflammation and apoptosis by activating the Nrf2. Thus, quercetin decreased intestinal free radical levels, inhibiting the phosphorylation of p38 and JNK. This study unveiled the harmful effects of aged-NPs on intestinal homeostasis and the practicability of dietary intervention against aged-NPs toxicity. These findings broaden the understanding of the NPs toxicity and provide an effective dietary strategy to relieve the health risks of NPs. ENVIRONMENTAL IMPLICATIONS: Growing levels of NPs pollution have represented severe health hazards to the population. This study focuses on the toxic mechanism of aged-NPs on the intestinal barrier and the alleviating effect of quercetin dietary intervention, which considers the environmental action and relevant dose. It revealed the harmful effects of aged-NPs on intestinal inflammation with the key point of free radical generation. Furthermore, a quercetin-rich diet holds significant promise for addressing and reversing intestinal damage caused by aged-NPs by maintaining intracellular redox homeostasis. These findings provide an effective dietary strategy to remediate human health risks caused by NPs.