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Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota
Siyue Wen1, Yu Zhao1, Shanji Liu1
1State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
Abstract:
Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180 μg/kg/day polystyrene MPs for 90 days, then intraperitoneally injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathological damage, inflammation and oxidative stress elicited by CTX were observed in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested positive association with aggravated hepatotoxicity via spearman correlation analysis. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the critical role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.
Insights
Chronic exposure to microplastics (MPs) exacerbates liver damage from chemotherapy drugs by disrupting the gut microbiome. This highlights the hidden health risks of MPs, especially when the body faces other toxic challenges.
Area of Science:
- Environmental Health
- Toxicology
- Gastroenterology
Background:
- Microplastics (MPs) are pervasive environmental contaminants with known health risks.
- The impact of MPs on liver resilience to external toxic stimuli is not well understood.
Purpose of the Study:
- To investigate if chronic microplastic exposure aggravates cyclophosphamide (CTX)-induced hepatotoxicity.
- To explore the role of gut microbiota and colonic integrity in MP-exacerbated liver injury.
Main Methods:
- A mouse model was established involving chronic oral exposure to polystyrene MPs (18 and 180 μg/kg/day for 90 days).
- Mice were subsequently injected with CTX (80 mg/kg) to assess liver injury.
- Gut microbiota composition, colonic permeability, inflammation, and oxidative stress were analyzed.
- Fecal microbiota transplantation (FMT) was used to confirm the role of gut bacteria.
Main Results:
- Mice pre-exposed to MPs showed significantly increased liver damage, inflammation, and oxidative stress following CTX treatment compared to controls.
- Chronic MP exposure led to colonic impairments, including a leaky gut, inflammation, and reduced antioxidant capacity.
- Gut microbiota alterations were observed, correlating positively with aggravated hepatotoxicity.
- FMT confirmed that MP-altered gut bacteria mediate increased liver susceptibility to CTX.
Conclusions:
- Chronic microplastic exposure can impair liver resistance to toxic insults, such as chemotherapy.
- The gut microbiome and colonic health play a critical role in mediating the exacerbated hepatotoxicity induced by microplastics.
- This study underscores the importance of considering combined exposures when assessing the health risks of microplastics.
