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Depression is not just a general mental health problem but a serious medical illness that can worsen without treatment. The gut microbiome plays a major role in the two-way communication system between the intestines and brain. The current study examined the effects of flavonoids on depression by observing the changes in the gut microbiome and depressive symptoms of young participants consuming flavonoid-rich orange juice. The depressive symptom was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), a psychiatric screening tool used to detect preexisting mental disorders. The study population was randomly divided into two groups: the flavonoid-rich orange juice (FR) and an equicaloric flavonoid-low orange cordial (FL) group. For 8 weeks, participants consumed FR (serving a daily 380 mL, 600 ± 5.4 mg flavonoids) or FL (serving a daily 380 mL, 108 ± 2.6 mg flavonoids). In total, 80 fecal samples from 40 participants (mean age, 21.83 years) were sequenced. Regarding depression, we observed positive correlations between brain-derived neurotrophic factor (BDNF) and the Lachnospiraceae family ( Lachnospiraceae_uc  and  Murimonas ) before flavonoid orange juice treatment. Most notably, the abundance of the Lachnospiraceae family ( Lachnospiraceae_uc ,  Eubacterium_g4 ,  Roseburia_uc ,  Coprococcus_g2_uc ,  Agathobacter_uc ) increased after FR treatment compared to that after FL treatment. We also validated the presence of unclassified Lachnospiraceae through sensitive real-time quantitative polymerase chain reaction using stool samples from participants before and after flavonoid treatment. Our results provide novel interventional evidence that alteration in the microbiome due to flavonoid treatment is related to a potential improvement in depression in young adults.

Flavonoid-Rich Orange Juice Intake and Altered Gut Microbiome in Young Adults with Depressive Symptom: A Randomized Controlled Study