In vivo methylmercury toxicity is exacerbated by polystyrene microplastic exposure, leading to colon barrier disruption, gut dysbiosis, and systemic oxidative imbalance

Methylmercury (MeHg) is a well-recognized toxicant, whereas microplastics (MP) are contaminants whose health effects continue to be explored. Evidence suggests that concomitant exposure to MeHg and polystyrene (PS) may enhance adverse outcomes in the gastrointestinal system. The aim of this study was to investigate the combined effects of MeHg and PS-MP on intestinal homeostasis, as well as systemic oxidative and inflammatory responses. A total of 64 rats with 30-days-old (n = 16 per group) were exposed to environmentally relevant doses of 0.5 mg/L MeHg and/or 0.2 mg/L PS-MP of 5 µm during 8 weeks. Co-exposure resulted in colon shortening, mucus depletion, and disruption of tight junction proteins, accompanied by macrophage infiltration and elevated pro-inflammatory cytokines. Structural and inflammatory changes were accompanied by gut dysbiosis, including altered microbial composition and reduced diversity indices. Biochemically, co-exposure amplified oxidative stress in the colon, with loss of free thiols and enhanced lipid peroxidation, while not markedly affecting glutathione-S-transferase activity. Systemically, combined treatment increased serum cytokines and induced genotoxicity. Although compensatory antioxidant responses were detected in blood, oxidative stress was evident in peripheral organs, particularly liver, kidneys, and heart. Taken together, these findings demonstrate that the intestine may be an early and sensitive target following co-exposure to MeHg and PS-MP, driving cytokine release into circulation and contributing to systemic injury. Our study provides novel in vivo evidence that combined PS-MP and MeHg exposure exacerbates some biological outcomes noted with individual contaminant exposure, indicating the importance of considering co-contamination scenarios in risk assessment of emerging pollutants.