Nobiletin is abundant in citrus peels and demonstrates good anti-
obesity bioactivity. However, its anti-
obesity mechanisms still remain unclear. This study aims to explore the bidirectional interaction between
nobiletin and gut microbiota in mice fed with a high-fat diet. For the colonic bioconversion, more demethylated metabolites with higher
biological activity were found in feces than
nobiletin in the 48 h excretion study and 8 week consecutive dosing study. Moreover, long-term oral intake of
nobiletin would modify the gut microbiota with improved demethylation ability and enhanced production of
short chain fatty acids. The comparison of metabolite profiles in mouse liver and feces indicated that gut microbiota might have a higher biotransformation activity on
nobiletin than the host. Two bacteria at the genus level, Allobaculum and Roseburia, remained enriched by
nobiletin after the 4- and 8-week feedings. They might correlate with the enhanced
nobiletin biotransformation and actively contribute to the health benefits of
nobiletin in vivo. These results suggested that the bidirectional interaction of
nobiletin and gut microbiota played an important role on the anti-
obesity effect of
nobiletin.