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Published on: February 27, 2014
Polystyrene microplastics trigger colonic inflammation in rats via the TLR4/NF-κB/COX-2 pathway and modulation of
Xuemin Feng1, Meng Zhang2, Tianyang Zhao2
1Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin 130021, China.
Abstract:
Polystyrene microplastics (PS-MPs) are common microplastics that pose significant health hazards to humans. Due to multifunctionality in the gut system, MP-associated damage and mechanisms require further exploration. This study was undertaken with the objective of elucidating the impact of PS-MP exposure on colonic inflammation in rats, and to explore its potential mechanisms. Forty-eight specific-pathogen-free Wistar male rats were administered 0, 0.5, 5, and 50 mg/kg/d of PS-MPs for 90 days, after which intestinal flora distribution, inflammatory factor levels in the colon, and TLR4/NF-κB/COX-2 gene levels were examined. To clarify whether PS-MPs directly infiltrate intestinal epithelial cells and induce cytotoxicity, human intestinal epithelial cells (HIECs) were exposed to a range of PS-MP concentrations (0 ∼ 100 microg/mL) for 48 h, and CCK-8 assays were conducted to assess the cell survival rates. In the colon tissue of rats exposed to PS-MP, goblet cells decreased, muscular layer arrangements were disordered, and disrupted and discontinuous crypt structures appeared in colon tissue, while high numbers of inflammatory cells infiltrated the colonic mucosa and submucosa. PS-MPs could accumulate in HIECs, and cell survival rates were decreased. In the colons of rats exposed to PS-MPs, the levels of Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were found to be elevated. Additionally, the mRNA and protein levels of TLR4/MyD88 in the colons of PS-MP-exposed rats exhibited a significant increase. Furthermore, the TLR4/NF-κB/COX-2 signaling pathway in rat colons was activated after MP exposure. When the TLR4/NF-κB/COX-2 signaling pathway was inhibited, the significant increases in IL-6 and TNF-α levels caused by PS-MPs were significantly reversed. PS-MP exposure also altered intestinal flora abundance in rats. Compared with the control group, the proportion of Firmicutes, Proteobacteria and Actinobacteria in PS-MPs exposed group was increased. In contrast, the proportion of Bacteroidetes and Verrucomicrobia decreased. Taken together, our results suggest that PS-MP could exert adverse effects on the gastrointestinal health of rats. Pro-inflammatory cytokine (IL-6, IL-1β and TNF-α) levels increased, and the TLR4/NF-κB/COX-2 signaling pathway was triggered. Thus, flora changes and increased intestinal inflammation may interact with each other.
Insights
Polystyrene microplastics (PS-MPs) cause gut inflammation and damage in rats by increasing pro-inflammatory cytokines and activating the TLR4/NF-κB/COX-2 pathway. Exposure also alters gut flora, suggesting a link between inflammation and microbial changes.
Area of Science:
- Environmental Health
- Toxicology
- Gastroenterology
Background:
- Polystyrene microplastics (PS-MPs) are prevalent environmental contaminants.
- Their impact on gastrointestinal health and underlying mechanisms require thorough investigation.
Purpose of the Study:
- To investigate the effects of PS-MP exposure on colonic inflammation in rats.
- To elucidate the molecular mechanisms, including the TLR4/NF-κB/COX-2 pathway and gut microbiota alterations, involved in PS-MP-induced gastrointestinal damage.
Main Methods:
- Rats were exposed to varying doses of PS-MPs for 90 days.
- Analysis included intestinal flora distribution, colonic inflammatory markers, and TLR4/NF-κB/COX-2 gene expression.
- Human intestinal epithelial cells (HIECs) were used to assess cytotoxicity and PS-MP accumulation.
Main Results:
- PS-MP exposure led to decreased goblet cells, disordered muscle layers, and disrupted crypt structures in rat colons.
- Accumulation of PS-MPs in HIECs reduced cell viability.
- Elevated levels of IL-1β, IL-6, and TNF-α were observed, alongside increased TLR4/MyD88 expression and TLR4/NF-κB/COX-2 pathway activation.
- Inhibition of this pathway reversed PS-MP-induced cytokine increases.
- Significant alterations in gut microbiota composition were noted, with increased Firmicutes and Proteobacteria, and decreased Bacteroidetes.
Conclusions:
- PS-MPs induce significant gastrointestinal damage and inflammation in rats.
- The TLR4/NF-κB/COX-2 signaling pathway is a key mediator of PS-MP-induced inflammation.
- Gut microbiota dysbiosis is associated with PS-MP exposure, potentially interacting with intestinal inflammation.

