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Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19-40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo- O -glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo- O -glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

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Stratification of Volunteers According to Flavanone Metabolite Excretion and Phase II Metabolism Profile after Single Doses of ‘Pera’ Orange and ‘Moro’ Blood Orange Juices