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Orange juice contains flavanones, which are associated with reducing the risk of obesityassociated diseases. We evaluated the effects of two varieties of orange juices on the oxidative stress, inflammatory response, and gut microbiota of individuals with insulin resistance and different obesity classes. In a randomized crossover study, obese patients consumed 'Pera' (POJ--source of flavanones) and 'Moro' (MOJ--source of flavanones and anthocyanins) orange juices for 15 days. Blood, urine, and fecal samples were collected before and after the intervention. Daily orange juice intake significantly reduced HDL and total cholesterol, in addition to urinary 8-OHdG and plasmatic MCP-1 levels. Multivariate analyses highlighted the beneficial effects of orange juice intake, mainly the modulation of inflammatory and oxidative stress biomarkers. Patients in different obesity classes presented a gut microbiota with obesity-associated alterations (dysbiosis), and the consumption of Pera and Moro orange juices improved this profile by modulating their gut microbiota in different ways. Although the Firmicutes/Bacteroidetes ratio changed after both interventions, MOJ provided more accentuated changes than POJ. Blautia, Bifidobacterium, and other genera had their relative abundance altered by juice consumption, which correlated with patient parameters (such as HDLcholesterol and diastolic blood pressure) and biomarkers (such as TNF-α and 8-OHdG). In conclusion, regular orange juice intake can be associated with a reduction in oxidative stress and inflammatory response, in addition to modulating gut microbiota. [ABSTRACT FROM AUTHOR]