Lignans are dietary polyphenols, which are metabolized by the gut microbiota into the
phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. The Breast
Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects plasma and
milk secretion of several drugs and natural compounds. We hypothesized here that Abcg2
could influence levels of lignans and their derived metabolites in target tissues.
Consequently, we aimed to evaluate the role of Abcg2 in the tissue distribution of these
compounds. We used Abcg2-/- knockout and wild-type male mice fed with a lignanenriched
diet for one week and analysed plasma, small intestine, colon, liver, kidneys and
testicles. High levels of lignans as well as enterolignans and their glucuronide and sulfate
conjugates in the small intestine and colon were detected, with higher concentrations of the
conjugates in the wild-type compared with Abcg2-/- mice. Particularly relevant was the
detection of 24-fold and 8-fold higher concentrations of enterolactone-sulfate and
enterolactone-glucuronide, respectively, in the kidney of Abcg2-/- compared with wild-type
mice. In conclusion, our study showed that lignans and their derived metabolites were in
vivo substrates of Abcg2, which affected their plasma and tissue levels. These results
highlight the role of Abcg2 in influencing the health-beneficial properties of dietary
lignans
