# Neonicotinoid pesticides disrupt gingival epithelial barrier function

## TL;DR

Neonicotinoid pesticides found in saliva disrupt a key protein in gum tissue, weakening the barrier against bacteria and potentially causing gum disease.

## Contribution

This study identifies a novel mechanism by which neonicotinoids impair gingival epithelial barrier function through CXADR mislocalization.

## Key findings

- Neonicotinoids were detected in saliva samples using high performance liquid chromatography.
- Neonicotinoids disrupt CXADR localization, increasing permeability to bacterial components like LPS and PGN.
- Lysosomal inhibition restores CXADR to the cell surface, suggesting a pathway for barrier disruption.

## Abstract

Neonicotinoid pesticides are highly persistent in the environment, with detection in periodontal blood reported. Although an association with gingival inflammation has been shown, the mechanism related to periodontal disease remains unclear. Previous study found that coxsackievirus and adenovirus receptor (CXADR) is involved in gingival tissue epithelial barrier function, thus the effects of neonicotinoids on CXADR were examined. High performance liquid chromatography of salivary samples from 16 volunteers detected acetamiprid, clothianidin, imidacloprid, and thiamethoxam. Administration of neonicotinoids (Σneonicotinoids) resulted in loss of cell-surface CXADR, which was restored by bafilomycin A1, a lysosomal inhibitor. Using a three-dimensional tissue model of human gingival epithelial cells, Σneonicotinoids were found to increase permeability to lipopolysaccharide (LPS) and peptidoglycan (PGN), which was dependent on CXADR. It is thus suggested that neonicotinoids cause mislocalization of CXADR into lysosomes, leading to gingival barrier function disruption, which allows for bacterial virulence factors to penetrate subepithelial tissues.

•Neonicotinoid pesticides can be detected in saliva of Japanese residents with high performance liquid chromatography.•Neonicotinoid disturbs intracellular transport of CXADR, a tight junction-related protein in gingival epithelial cells.•Neonicotinoid pesticides increase permeability of gingival epithelial tissues to lipopolysaccharide and peptidoglycan.

Neonicotinoid pesticides can be detected in saliva of Japanese residents with high performance liquid chromatography.

Neonicotinoid disturbs intracellular transport of CXADR, a tight junction-related protein in gingival epithelial cells.

Neonicotinoid pesticides increase permeability of gingival epithelial tissues to lipopolysaccharide and peptidoglycan.