Abstract
As two representative environmental contaminants, the individual toxic effects of microplastics and triclosan have been extensively studied; however, systematic evidence regarding their combined toxicity in mammals and the underlying mechanisms remains lacking. In this study, mice were orally exposed to triclosan (TCS) or/and polystyrene microplastics (PS), and their toxicity to intestine and liver was evaluated through histopathological examination, biochemical assays, and 16S rRNA sequencing. Results demonstrated that co-exposure to TCS and PS elicited markedly aggravated toxicological effects compared to individual exposures. Histopathological evaluation revealed exacerbated tissue damage, with histological scores substantially higher in co-exposed mice (colon: 7.27; liver: 5.0) than in PS-alone (colon: 6.07; liver: 3.0) or TCS-alone (colon: 3.0; liver: 0.7) groups. Quantitative Integrated Biomarker Response (IBR) analysis confirmed this potential additive or synergistic interaction: co-exposure not only dramatically elevated colonic oxidative stress (R(IB) = 12.30 vs. 5.88 in PS and 0.23 in TCS groups) but also exacerbated inflammatory responses (R(IB) = 11.69 vs. 3.52 in PS and 0 in TCS). Hepatic assessment demonstrated the most severe compromise in liver function and oxidative homeostasis following co-exposure (R(IB) = 16.48), markedly exceeding the effects of individual PS (4.75) or TCS (0.43) exposure. In-depth exploration found that co-exposure to TCS and PS significantly disrupted gut microbiota homeostasis, characterized by enrichment of opportunistic pathogens and depletion of short-chain fatty acid-producing bacteria; these alterations were not only correlated with intestinal barrier impairment but also exacerbated gut-liver axis dysregulation. Together, the findings not only highlight the synergistic toxicity of triclosan and polystyrene microplastics in mice but also identify the gut-liver axis as a mediator of this effect, thereby providing novel evidence for health risk assessment and underscoring a potential concern for human health under co-exposure.