Gut microbiota contributes to polystyrene nanoplastics-induced fetal growth restriction by disturbing placental nicotinamide metabolism

Polystyrene nanoplastics (PS-NPs) are ubiquitous in the environment, eliciting significant concerns about their possible risks to human health, especially reproductive health. Various reproductive toxicities of PS-NPs have been reported, however, information regarding the effects of PS-NPs exposure during pregnancy on offspring development and the underlying mechanisms remains limited. In this study, pregnant mice were orally administered PS-NPs (approximately 100 nm in diameter) at different concentrations (1, 10, and 100 mg/kg/day) for 17.5 consecutive days, from gestational day (GD) 0.5 to GD 17.5. The relevant samples were collected on GD 18.5 to investigate the intergenerational effects. The results indicated that PS-NPs induced placental injury and metabolic abnormalities, leading to adverse pregnancy outcomes. Specifically, PS-NPs exposure observably reduced the levels of nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD⁺) in the placenta, resulting in decreased ATP production, increased oxidative stress and ferroptosis. Meanwhile, PS-NPs disrupted the maternal gut microbiome, specifically manifested as a reduction in Lactobacillus levels and abundances of norank_f_Muribaculaceae, Turicibacter, Alloprevotella, Parabacteroides and Ruminococcus. Fecal microbial transplant (FMT) experiments demonstrated that the microbiota from PS-NPs-administered pregnant mice could similarly induce intestinal barrier damages and placental injury. Treatment with NAM effectively mitigated disruptions in placental metabolism and reversed the adverse pregnancy outcomes caused by PS-NPs. These findings highlight the novel role of the gut microbiota in PS-NPs-induced placental injury and adverse pregnancy outcomes, and suggest that NAM could serve as a promising preventative strategy against this intergenerational damage caused by PS-NPs.