Demethylation of Polymethoxyflavones by Human Gut Microbiome (LB601)

Abstract

Polymethoxyflavones (PMFs) are dietary flavonoid found in citrus fruit and have been shown to have various health promoting bioactivities. Our previous research has demonstrated that biotransformation of PMFs by gut microbiome play important role in their bioactivities. For example, glucuronide and sulfate conjugates of PMFs can be deconjugated to produce metabolites with much stronger bioactivities. Herein, we further investigated the biotransformation of PMFs by gut microbiome. Major PMFs, i.e. Nobiletin (NBT) and 5‐hydroxylnobiletin (5HN), and their six metabolites were anaerobically fermented with colonic microbiome freshly isolated from human volunteers. HPLC analysis was utilized to monitor the levels of these PMFs and the production of new metabolites. The results showed that 3’ and 4’‐hydroxylnobiletin can be demethylated to 3’, 4’‐ dihydroxylnobiletin (DHN); while 5, 3’ and 5, 4’‐ dihydroxylnobiletin can be demethylated to 5, 3’, 4’‐ trihydroxylnobiletin (THN) by human colonic microbiome. However, in term of demethylation, colonic microbiome had no effect on NBT, 5HN, DHN and THN. Our results further demonstrated that the extent of demethylation varied considerably among the microbiome isolated from different human subjects. This study provided important leads for further investigation on the bioactivities of PMFs.