Nanoplásticos de poliestireno como moduladores do eixo microbiota-intestino-cérebro: implicações na disbiose e no estresse oxidativo em camundongas em diferentes fases do desenvolvimento

Abstract

The environmental dissemination of micro- and nanoplastics (MNPs) has raised growing concerns regarding their impact on human health and the integrity of the microbiota-gut-brain axis. This study evaluated the effects of repeated oral exposure to polystyrene nanoplastics (100 nm, 40 mg/kg) over 21 days in late young (n=16) and pre-pubertal (n=15) female Swiss mice. Two cohorts underwent a battery of behavioral tests, including the Open Field Test and Forced Swim Test. Following euthanasia, fecal samples were collected for microbiota analysis via qPCR, and brain tissues—specifically the hippocampus (HP), prefrontal cortex (PFC), and striatum (STR)—were harvested to quantify biomarkers of oxidative and nitrosative stress. The results demonstrated that while there were no alterations in global locomotion or classical anxiety- and depression-like behaviors, exposed pre-pubertal animals showed a significant increase in peripheral rearing ($p=0.0252$) and grooming ($p<0.05$), indicating an age-dependent selective modulation of exploratory and emotional behavior. Regarding the gut microbiota, no changes were detected in the isolated abundances of Firmicutes or Bacteroidetes; however, a reduction in the Firmicutes/Bacteroidetes ratio was observed in both exposed groups ($p=0.0101$), suggesting the presence of subtle dysbiosis. Distinct vulnerabilities to nitrosative stress were observed according to the life stage: pre-pubertal animals exhibited a robust increase in nitrite levels (p=0.0017), whereas late youngs displayed a compensatory increase in reduced glutathione (GSH) (p=0.0136) within the hippocampus. In conclusion, repeated exposure to nanoplastics promotes low magnitude yet selective effects, with greater neurobehavioral and nitrosative vulnerability during the pre-pubertal stage. These findings provide evidence supporting the involvement of the microbiota-gut-brain axis in the toxicity of these emerging pollutants.