Impact of dietary and microbial fatty acids on the bioavailability of phenolics

The current work addresses the possible impact of dietary and microbial fatty acids on the absorption of phenolics at the intestinal epithelium. The Caco-2 cell culture model of small intestinal enterocytes was optimised to mimic the chronic supplementation with physiological concentrations of fatty acid. Treatment with polyunsaturated fatty acids (PUFA) changed the fluidity of the brush border membrane, but this modification did not affect transepithelial transport of the test compounds caffeic acid, ferulic acid and epicatechin. PUFA supplementation did however increase paracellular diffusion of caffeic acid and epicatechin in apical to basolateral (a→b) transport direction. Epicatechin efflux was reduced by arachidonic acid and decosahexaenoic acid (DHA) supplementation, most likely by reducing either expression or activity of the ATP-binding cassette transporter family member C2. Transepithelial transport of ferulic acid in a→b direction was increased by PUFA supplementation, most likely through upregulation of an apical uptake transporter, whose identity could not be determined here. Supplementation of cells with the microbial metabolite butyric acid upregulated gene expression of monocarboxylate transporters 1 and 4, which resulted in increased ferulic acid uptake and metabolism. Metabolism of epicatechin was also affected by PUFA supplementation of cells. An unusual pattern of epicatechin glucuronidation by UDP-glucuronosyl transferase (UGT) 1A8 was observed in the intestinal cell line HT29-MTX. UGT activity was highly polarised within the cell, resulting in up to fifty times higher metabolite levels when the substrate reached the cell layer from what in vivo would be the serosal side, than from the side corresponding to the intestinal lumen. Consequent immunofluorescence staining revealed the presence of UGT1A8 in the basolateral plasma membrane. These in vitro results suggest a possible impact of dietary and microbial fatty acids on the absorption and metabolism of phenolic compounds.