Higher baseline expression of the PTGS2 gene and greater decreases in total colonic fatty acid content predict greater decreases in colonic prostaglandin-E2 concentrations after dietary supplementation with ω-3 fatty acids

Abstract This study evaluated whether mRNA expression of major genesregulating formation of prostaglandin (PG)E 2 in the colonand colonicfatty acid concentrations are associated with the reduction in colonicmucosal PGE 2 after dietary supplementation with omega-3 (ω-3) fatty acids. Supplementation with ω-3 fatty acids was done for 12 weeks using personalized dosing that was expected to reduce colonicPGE 2 by 50%. In stepwise linear regression models, the ω-3 fatty acid dose and baseline BMI explained 16.1% of the inter-individual variability in the fold changeof colonicPGE 2 post-supplementation. Increases in mRNA gene expression after supplementation were, however, modest and were not associated with changes in PGE 2 . When baseline expression of PTGS1, PTGS2 and HPGD genes was included in the linear regression model containing dose and BMI, only PTGS2 , the gene coding for the inducible form cyclooxygenase, was a significant predictor. Higher relative expression of PTGS2 predicted greater decreases in colonicPGE 2 , accounting for an additional 13.6% of the inter-individual variance. In the final step of the regression model, greater decreases in total colonicfatty acid concentrations predicted greater decreases in colonicPGE 2 , contributing to an additional 18.7% of the variance. Overall, baseline BMI, baseline expression of PTGS2 and changes in colonictotal fatty acids together accounted for 48% of the inter-individual variability in the change in colonicPGE 2 . This is consistent with biochemical data showing that fatty acids which are not substrates for cyclooxygenasescan activate cyclooxygenase-2 allosterically. Further clinical trials are needed to elucidate the factors that regulate the fatty acid milieu of the human colonand how this interacts with key lipid metabolizing enzymes. Given the central role of PGE 2 in coloncarcinogenesis, these pathways may also impact on coloncancer prevention by other dietary and pharmacological approaches.