Anti-Inflammatory Implications of the Microbial Transformation of Dietary Phenolic Compounds

Abstract

Due to the success of therapeutic anti-inflammatory compounds to inhibit, retard, and reverse the development of colon cancer, the identification of dietary compounds as chemopreventives is being vigorously pursued. However, an important factor often overlooked is the metabolic transformation of the food-derived compounds in the gut that may affect their bioactivity. Commonly consumed dietary phenolics (esterified ferulic acid and its 5-5′-linked dimer), which have the potential to undergo predominant microbial transformations (de-esterification, hydrogenation, demethylation, dehydroxylation, and dimer cleavage), were incubated with human microbiota. The metabolites were identified (high-performance liquid chromatography and nuclear magnetic resonance) and confirmed to be present in fresh fecal samples from 4 human volunteers. The potential anti-inflammatory properties were compared by measuring the ability of the parent compounds and their metabolites to modulate prostanoid production in a cell line in which the inflammatory pathways were stimulated following a cytokine-induced insult. The compounds were readily de-esterified and hydrogenated, but no dimer cleavage occurred. Only the monomer underwent demethylation and selective de-hydroxylation. The resultant metabolites had differing effects on prostanoid production ranging from a slight increase to a significant reduction in magnitude. This suggests that the microbial transformation of dietary compounds will have important inflammatory implications in the chemoprevention of colon cancer.

ACKNOWLEDGMENTS

Funding is gratefully acknowledged from the Scottish Executive Environment and Rural Affairs Department (SEERAD).

Notes

^a Abbreviation is as follows: IUPAC, International Union of Pure and Applied Chemistry. Samples were obtained from 4 volunteers consuming an unrestricted Western-style diet. Concentration in fecal waters is given as mean ± SDs (n = 4).

^a Abbreviation is as follows: IUPAC, International Union of Pure and Applied Chemistry. Human colon fibroblast cells at passage 5; population doubling 27 (P5) were treated with phytochemicals (compounds 2–13; 0.1 μmol dm⁻³) 30 min prior to cytokine stimulation. Prostanoid concentration was measured after 2 h stimulation with IL-1β (10 ng cm⁻³). Values are given as mean ± SDs (n = 3). Significant differences between the IL-1β-stimulated cells and IL-1β-stimulated cells in the presence of phytochemicals were determined by the t-test (ρ).