# Nanoplastic Disrupts Intestinal Homeostasis in Immature Rats by Altering the Metabolite Profile and Gene Expression

## TL;DR

Nanoplastics disrupt gut health in young rats by altering gene activity and metabolite levels, leading to inflammation and oxidative stress.

## Contribution

This study reveals how nanoplastics affect intestinal function in immature rats through molecular and metabolomic changes.

## Key findings

- PS-NPs accumulated in the intestinal epithelium and altered gene expression related to gut barrier and nutrient absorption.
- Exposure increased proinflammatory cytokines and oxidative damage while reducing antioxidant capacity.
- Metabolomic changes included altered amino acid profiles linked to inflammation, energy, and protein synthesis.

## Abstract

Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms.