Kankul K.Chaimon S.Prathaphan P.Tanramluk D.Sanannam B.Thongsepee N.Sangpairoj K.Phannasil P.Phasai S.Adisakwattana P.Chantree P.Martviset P.Mahidol University2026-05-252026-05-252026-07-01Veterinary Parasitology Vol.345 (2026)03044017https://repository.li.mahidol.ac.th/handle/123456789/116838Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a major parasitic disease of livestock and humans. The increasing reports of drug resistance emphasize the need for novel therapeutic targets. However, before identifying a drug target, the parasite's biological processes need to be understood. F. gigantica, the predominant species in Asia, inhabits the bile duct, suggesting adaptation to bile-rich environments. We previously reported the discovery of a type-1 nuclear receptor from F. gigantica (FgNR1). We hypothesized that it functions as a bile salt–responsive transcription factor essential for parasite biology, but the exact functions have never been reported. Sequence analysis revealed that the ligand-binding domain (LBD) of FgNR1 (FgNR1-LBD) contains a conserved nuclear receptor signature motif (Tτ) and shares high homology with bile salt–responsive nuclear receptors in mammals, indicating conserved ligand recognition mechanisms. Using a luciferase reporter assay in a double-stable mammalian cell system, we demonstrate that the bile salts taurocholic acid (TCA) and glycocholic acid (GCA) significantly activate FgNR1-LBD–dependent transcriptional activity. Consistently, molecular docking analyses showed strong binding affinities of these bile salts within the predicted ligand-binding pocket of FgNR1-LBD. These findings provide the first functional evidence for bile salt regulation of gene expression via FgNR1. Importantly, this study establishes FgNR1-LBD as a tractable, parasite-specific molecular target, providing a foundation for understanding host-parasite interactions and furthering the discovery of agonists, antagonists, or inhibitors to disrupt parasite biological processes.Immunology and MicrobiologyVeterinaryArticleSCOPUS10.1016/j.vetpar.2026.1108002-s2.0-10503883840318732550