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<p>Bifenthrin (BF) is a widely used pyrethroid insecticide and is recognized as an endocrine-disrupting chemical (EDC). Accumulating evidence indicates that long-term exposure to BF can induce a variety of adverse health outcomes. However, its potential role in the pathogenesis of ulcerative colitis (UC) remains elusive. In this study, we integrated data from multiple databases—including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH—to predict potential molecular targets of BF. UC-associated genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), DisGeNET, Therapeutic Target Database (TTD), and DrugBank. Candidate targets were identified by intersecting predicted BF targets with UC-related genes, followed by functional enrichment analysis using DAVID. The STRING database and Cytoscape software were employed to construct protein-protein interaction (PPI) networks and screen for hub genes. A diagnostic model based on these hub genes was established and validated using the GSE47908 and GSE13367 datasets. Additionally, immune infiltration analysis was performed to compare the UC group with controls, identifying immune cell types significantly associated with the target genes. Molecular docking simulations via AutoDock Vina were conducted to evaluate the binding affinities between BF and the five hub proteins. Functional analysis revealed that the candidate genes were primarily enriched in pathways related to oxidative stress and inflammatory responses. Five core hub genes—<i>BCL2</i>, <i>TP53</i>, <i>TNF</i>, <i>IL6</i>, and <i>PTGS2</i>—were consistently identified across all analytical platforms. In vitro experiments demonstrated that BF exposure significantly exacerbated colonic inflammation by downregulating anti-inflammatory/apoptotic genes (<i>BCL2, TP53</i>) and upregulating pro-inflammatory markers (<i>IL6</i>, <i>TNF</i>, <i>PTGS2</i>). Collectively, our findings suggest that bifenthrin may promote colorectal inflammation by dysregulating key genes and modulation of the pro-inflammatory immune microenvironment, thus providing novel insights into the environmental etiology of UC.</p>

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Bifenthrin exacerbates ulcerative colitis via immunotoxicity: network toxicology and experimental validation reveal novel therapeutic targets

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • Lingxiao Wang,
  • Weixing Zhang,
  • Yifan Kang,
  • Yaoping Li

摘要

Bifenthrin (BF) is a widely used pyrethroid insecticide and is recognized as an endocrine-disrupting chemical (EDC). Accumulating evidence indicates that long-term exposure to BF can induce a variety of adverse health outcomes. However, its potential role in the pathogenesis of ulcerative colitis (UC) remains elusive. In this study, we integrated data from multiple databases—including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH—to predict potential molecular targets of BF. UC-associated genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), DisGeNET, Therapeutic Target Database (TTD), and DrugBank. Candidate targets were identified by intersecting predicted BF targets with UC-related genes, followed by functional enrichment analysis using DAVID. The STRING database and Cytoscape software were employed to construct protein-protein interaction (PPI) networks and screen for hub genes. A diagnostic model based on these hub genes was established and validated using the GSE47908 and GSE13367 datasets. Additionally, immune infiltration analysis was performed to compare the UC group with controls, identifying immune cell types significantly associated with the target genes. Molecular docking simulations via AutoDock Vina were conducted to evaluate the binding affinities between BF and the five hub proteins. Functional analysis revealed that the candidate genes were primarily enriched in pathways related to oxidative stress and inflammatory responses. Five core hub genes—BCL2, TP53, TNF, IL6, and PTGS2—were consistently identified across all analytical platforms. In vitro experiments demonstrated that BF exposure significantly exacerbated colonic inflammation by downregulating anti-inflammatory/apoptotic genes (BCL2, TP53) and upregulating pro-inflammatory markers (IL6, TNF, PTGS2). Collectively, our findings suggest that bifenthrin may promote colorectal inflammation by dysregulating key genes and modulation of the pro-inflammatory immune microenvironment, thus providing novel insights into the environmental etiology of UC.