Sex-specific effects of polystyrene microplastics and lead co-exposure on the gut microbiome and fecal metabolome in C57BL/6 mice

The widespread of microplastics has gained growing public health concerns globally. Due to their porous structure and large surface area, microplastics could serve as a carrier for other environ-mental pollutants, including heavy metals. Although the toxic effect of microplastics or heavy metals have been reported previously, investigations on the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In present study, the effects of polystyrene microplastics and lead co-exposure on the gut microbiome, intestinal permeability and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead increased the intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.