# Mechanistic evidence for dibutyl phthalate as an environmental trigger for inflammatory bowel disease

## TL;DR

The study shows how dibutyl phthalate (DBP) can trigger intestinal inflammation linked to inflammatory bowel disease (IBD) through specific molecular mechanisms.

## Contribution

The novel use of network toxicology and functional validation identifies LCN2 as a key mediator of DBP-induced inflammation in IBD.

## Key findings

- DBP exposure upregulates a six-gene signature in human colonic epithelial cells.
- LCN2 silencing significantly reduces DBP-induced inflammation.
- The study confirms a mechanistic link between DBP and IBD pathways.

## Abstract

Dibutyl phthalate (DBP) is a ubiquitous pollutant, but its molecular link to inflammatory bowel disease (IBD) is undefined. We employed an integrative network toxicology framework, combining DBP target databases with IBD patient transcriptomics to address this gap. A computational pipeline using machine learning and molecular docking predicted a core six-gene signature (KYNU, PCK1, LCN2, CDC25B, EPHB4, SORD). We validated these predictions in human colonic epithelial cells (NCM460). DBP exposure induced a pro-inflammatory state and upregulated the core genes, with LCN2 showing the strongest response. Crucially, siRNA-mediated silencing of LCN2 significantly attenuated the DBP-induced inflammatory response, establishing it as a key functional mediator. Our findings provide direct mechanistic insight into how DBP can promote intestinal inflammation. The functional validation of LCN2 confirms the predictive power of our integrated approach and identifies a panel of target genes for future IBD investigation and environmental risk assessment.

•Network toxicology links dibutyl phthalate (DBP) to IBD molecular mechanisms•DBP perturbs pathways of inflammation, lipid metabolism, and matrix remodeling•Silencing the core target LCN2 attenuates DBP-induced inflammation in colon cells•The findings provide a basis for the environmental risk assessment of DBP in IBD

Network toxicology links dibutyl phthalate (DBP) to IBD molecular mechanisms

DBP perturbs pathways of inflammation, lipid metabolism, and matrix remodeling

Silencing the core target LCN2 attenuates DBP-induced inflammation in colon cells

The findings provide a basis for the environmental risk assessment of DBP in IBD

Toxicology; Environmental toxicology