Bisphenol Exposure Linked to Inflammatory Bowel Disease Through RORC Immune Pathway

A new study published in Environmental Sciences Europe reports that bisphenols, a widely used family of environmental chemicals with endocrine-disrupting and immunotoxic potential, may be molecularly connected to inflammatory bowel disease (IBD) through the immune-related gene RORC. The research, published on 16 October 2026, combined computational network toxicity, multi-omics analyses, and laboratory experiments to trace how BP exposure might influence inflammatory responses relevant to IBD.

The researchers first identified fifty genes overlapping between BP-related targets and IBD-related genes. These shared genes were mainly enriched in IL-17 and TNF signaling pathways, oxidative stress, and lipid metabolic processes. To narrow down which of these genes were most plausibly involved, the team applied Mendelian randomization combined with bulk RNA-seq data, which prioritized FTO, CDH1, and RORC as candidate genes. Further sensitivity analyses using SMR methods provided additional support for RORC and CDH1.

Colocalization analysis offered the study’s strongest genetic evidence: it found shared causal variants between RORC expression and IBD risk, with a posterior probability of H4 (PPH4) of 0.934. On this basis, the authors highlighted RORC as the key candidate gene linking BP exposure to IBD risk. Immune infiltration and single-cell analyses suggested that RORC was related to CD4+ T-cell-associated immune regulation in IBD, pointing to a possible immune-mediated mechanism.

To explore whether bisphenols could physically interact with the RORC protein, the researchers performed molecular docking, which predicted favorable interactions between RORC and BPs. The team then turned to an in vitro model: HT29 cells, an epithelial cell line, were stimulated with IL-17A to mimic inflammatory signaling, and the effect of BP exposure on epithelial inflammatory responses was assessed.

In these cell experiments, bisphenol A (BPA) further enhanced IL-17A-induced epithelial inflammatory responses. The observed effects included increased chemokine production and activation of inflammatory signaling pathways in the exposed cells. The authors note that these findings suggest BPs may promote IBD-related inflammatory responses through immune-associated mechanisms, with RORC as a central candidate in that process.

The study’s conclusions are framed carefully by its design. The genetic analyses identify statistical associations and shared causal variants between gene expression and disease risk, while the cell-based experiments demonstrate effects in a laboratory model rather than in patients. The authors state that RORC may be a key immune-related candidate linking BP exposure to IBD risk, a formulation that reflects the inferential nature of the combined evidence rather than a demonstrated causal chain in humans.

As an open-access article shared early under Springer’s in-progress publication process, the paper is citable with a permanent DOI, though the published version remains subject to further editorial edits before the final Version of Record replaces it.

Subject of Research: Genetic and toxicological links between bisphenol exposure and inflammatory bowel disease centered on the RORC gene

Article Title: RORC-centered genetic and toxicological signatures connect bisphenols to inflammatory bowel disease

Article References: Wang, L., Liu, X., Qin, M., Diao, Y., Wang, L., Liu, X., Xiang, C., Zhao, J., Chen, B., & Peng, D. (2026). RORC-centered genetic and toxicological signatures connect bisphenols to inflammatory bowel disease. Environmental Sciences Europe. https://doi.org/10.1186/s12302-026-01546-x

Image Credits: AI Generated

DOI: 10.1186/s12302-026-01546-x

Keywords: bisphenols, BPA, inflammatory bowel disease, RORC, Mendelian randomization, colocalization, IL-17 signaling, CD4+ T cells, HT29 cells, molecular docking, endocrine disruptors, multi-omics