INTRODUCTION: Bile acids, classically known for their roles in fat digestion, are now recognised as important regulators of many aspects of intestinal physiology, including mucosal immune responses, epithelial proliferation/apoptosis, and transepithelial transport and barrier function. Therefore, the nuclear bile acid receptor, farnesoid X receptor (FXR), represents a promising therapeutic target for intestinal disorders, such as inflammatory bowel disease and colorectal cancer. Previous studies suggest that a particular class of plant-derived phytochemicals modulates FXR activity. AIMS AND METHODS: Here we set out to investigate the effects of a phytochemical, denoted KFS1, on FXR signalling in colonic epithelia. T84 colonic epithelial cells, grown as polarised monolayers, were treated bilaterally with the FXR agonist, GW4064 (5 μM) and KFS1 (1 – 100 μM) for 24 hrs. Expression of FXR and FGF-19, an index of FXR activation, were measured by qRT-PCR and ELISA. Transepithelial electrical resistance (TEER) was measured as an index of epithelial integrity. Lactate dehydrogenase (LDH) release was used as a measure of cytotoxicity. Data are expressed as the mean ± SEM for a series of n experiments. RESULTS: GW4064 (5 µM) induced a 719.8 ± 183.3 fold increase in FGF-19 mRNA expression (n = 20; p<0.001) and a 100 ± 24.6 pg/ml increase in FGF-19 protein expression (n = 5; p<0.01). KFS1 (1 – 100 μM) did not significantly increase FGF-19 protein expression and at higher concentrations (50 – 100 µM) reduced TEER. Lower concentrations of KFS1 (5 – 10 µM) did not alter TEER but significantly increased FXR mRNA expression by 4.16 ± 0.4 and 3.3 ± 0.4 fold, respectively (p<0.05; n = 4). Moreover, pre-treatment of T84 cells with KFS1 (1, 5, or 10 µM) for 1 hr prior to treatment with GW4064 (5 µM; 24 hrs) potentiated GW4064-induced FGF-19 mRNA expression by 2.5 ± 0.8, 2.9 ± 0.2, and 4.6 ± 0.5 fold, respectively (p<0.01; n = 6) and FGF-19 protein expression by 292.4 ± 52.7, 477.3 ± 66.5, and 530.3 ± 61.8 pg/ml, respectively (p<0.05; n=7). Combined treatment with KFS1 (1, 5, 10 µM and 50 µM) and GW4064 (5 µM) for 24 hrs also reduced TEER to 49.8 ± 7.4%, 50.6 ± 8.3%, 40.6 ± 6.6% and 37.2 ± 10 % of control values, respectively (n=7). Only at the highest concentration of KFS1 tested (50 µM), did co-treatment with GW4064 increase LDH release (p<0.01; n=5). Finally, a methanolic extract of plant material known to be rich in KFS1 (denoted QE1) was prepared. Similar to KFS1, QE1 (100 µg/ml) increased GW4064-induced FGF-19 release from T84 cells to 309.3 ± 18.9 pg/ml compared to 171.1 ± 34.1 pg/ml in controls (n = 6; p<0.01). CONCLUSION: Our data suggest that KFS1, a common dietary phytochemical, increases FXR expression in colonic epithelial cells, an effect which may prime cells for agonist-induced FXR activation. These findings suggest that foods, or food supplements, rich in such plant-derived phytochemicals have potential for development as FXR-targeted neutraceuticals.