Long-term exposure to polystyrene microplastics promotes HFD-induced obesity in mice through exacerbating microbiota dysbiosis

Abstract Background: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to MPs and its effects on the development of obesity are not yet fully understood. This study aimed to investigate the effect of polystyrene (PS)-MPs exposure on high fat diets (HFD)-induced obesity and underlying mechanisms. Methods: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence PS-MPs via oral administration for 8 weeks. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MPs on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies, and investigated the dysbiosis-associated mucous layer damage and systemic inflammation. Results: We found that PS-MPs supplementation led to an increased body weight, increases of liver weight, development of hepatic steatosis, elevated tissues mass of white adipose, and induced glucose intolerance and hyperlipemia. At the molecular level, PS-MPs administration was associated with enhanced protein levels of C/EBPα and PPARγ two critical transcription factors that regulate lipid metabolism in the liver, while reducing the protein level of PGC-1α in HFD-fed mice. Furthermore, 16S rRNA sequencing of the fecal microbiota indicated that PS increased the diversity and changed composition of the gut microbiota in HFD-fed mice. Potential relations analysis revealed that PS induced microbiota dysbiosis was associated with obesity.Interestingly, microbiota-depleted mice were resistance to PS-induced obesity, suggesting that intestinal microbiota played a critical role in PS-induced obesity pathogenesis. Importantly, transplantation of PS-altered microbiota to microbiota-depleted HFD-fed mice promoted colon mucus layer damage, systematic inflammation and obesity. Conclusions: Our findings provide a new gut microbiota-driven mechanism for PS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly existed in daily life, particularly in susceptible population.