Figure 1. CONSORT flow diagram. FR group: flavonoid-rich orange juice group; FL group: flavonoid-low orange cordial group.

Figure 1. CONSORT flow diagram. FR group: flavonoid-rich orange juice group; FL group: flavonoid-low orange cordial group.

Figure 2. Difference between flavonoid-rich orange juice group or flavonoid-low orange cordial group in plasma levels before and after intervention. (a) fatty acid-binding protein-2 (FABP2) (b) LPS endotoxin (c) BDNF (d) Zonulin (e) Claudin-5. After 8 weeks of orange juice intervention, the blood markers of human FABP2 in the flavonoid-rich group decreased significantly compared to those of the flavonoid-low groups. In contrast, the BDNF and Zonulin in the flavonoid-rich group were increased significantly compared to those in flavonoid-low groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. * p < 0.05; ** p < 0.01; **** p < 0.0001.

Figure 2. Difference between flavonoid-rich orange juice group or flavonoid-low orange cordial group in plasma levels before and after intervention. (a) fatty acid-binding protein-2 (FABP2) (b) LPS endotoxin (c) BDNF (d) Zonulin (e) Claudin-5. After 8 weeks of orange juice intervention, the blood markers of human FABP2 in the flavonoid-rich group decreased significantly compared to those of the flavonoid-low groups. In contrast, the BDNF and Zonulin in the flavonoid-rich group were increased significantly compared to those in flavonoid-low groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. * p < 0.05; ** p < 0.01; **** p < 0.0001.

Figure 3. Differences between flavonoid-rich orange juice group or flavonoid-low orange cordial group before and after the intervention. (a,b) Post-intervention, the HAMD-17 and BDI-II scores in the AFR and AFL groups decreased significantly (p < 0.0001) compared to those of the BFR and BFL groups. (c) CES-D scores in the AFR (p < 0.0001) and AFL (p < 0.001) decreased significantly compared to those of the BFR and BFL groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. BDI-II, Beck Depression Inventory-II; CES-D, Center for Epidemiological Studies Depression Scale; HAMD, Hamilton Depression Rating Scale. *** p < 0.001; **** p < 0.0001.

Figure 3. Differences between flavonoid-rich orange juice group or flavonoid-low orange cordial group before and after the intervention. (a,b) Post-intervention, the HAMD-17 and BDI-II scores in the AFR and AFL groups decreased significantly (p < 0.0001) compared to those of the BFR and BFL groups. (c) CES-D scores in the AFR (p < 0.0001) and AFL (p < 0.001) decreased significantly compared to those of the BFR and BFL groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. BDI-II, Beck Depression Inventory-II; CES-D, Center for Epidemiological Studies Depression Scale; HAMD, Hamilton Depression Rating Scale. *** p < 0.001; **** p < 0.0001.

Figure 4. Differences between flavonoid-rich orange juice group or flavonoid-low orange cordial group in short-chain fatty acids (SCFAs) from before and after intervention with flavonoid-rich (BFR & AFR) or flavonoid-low (BFL & AFL) orange juice. AA: acetic acid (a), PA: propionic acid (b), BA: butyric acid (c), VA: valeric acid (d), iso-VA: iso-valeric acid (e), iso-BA: iso-butyric acid (f). BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. * p < 0.05; ** p < 0.01; *** p < 0.001.

Figure 4. Differences between flavonoid-rich orange juice group or flavonoid-low orange cordial group in short-chain fatty acids (SCFAs) from before and after intervention with flavonoid-rich (BFR & AFR) or flavonoid-low (BFL & AFL) orange juice. AA: acetic acid (a), PA: propionic acid (b), BA: butyric acid (c), VA: valeric acid (d), iso-VA: iso-valeric acid (e), iso-BA: iso-butyric acid (f). BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group. * p < 0.05; ** p < 0.01; *** p < 0.001.

Figure 5. Differences between the taxonomic composition of before and after flavonoid-rich orange juice group and flavonoid-low orange cordial group intervention in depression. Lefse (a,c) and LDA analysis score (b,d) show the difference in abundance of bacterial taxa between before and after intervention with flavonoid-rich orange juice groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group.

Figure 5. Differences between the taxonomic composition of before and after flavonoid-rich orange juice group and flavonoid-low orange cordial group intervention in depression. Lefse (a,c) and LDA analysis score (b,d) show the difference in abundance of bacterial taxa between before and after intervention with flavonoid-rich orange juice groups. BFR: Before flavonoid-rich orange juice group, AFR: after flavonoid-rich orange juice group, BFL: before flavonoid-low orange cordial group, AFL: after flavonoid-low orange cordial group.

Figure 6. Differences between the taxonomic composition of after flavonoid-low orange juice group and flavonoid-rich orange cordial group intervention in depression. Lefse (a) and LDA analysis score (b) present the differences in the abundance of bacterial taxa after intervention between the flavonoid-low orange juice and flavonoid-rich orange cordial groups, respectively. AFL: after flavonoid-low orange cordial group, AFR: after flavonoid-rich orange juice group.

Figure 6. Differences between the taxonomic composition of after flavonoid-low orange juice group and flavonoid-rich orange cordial group intervention in depression. Lefse (a) and LDA analysis score (b) present the differences in the abundance of bacterial taxa after intervention between the flavonoid-low orange juice and flavonoid-rich orange cordial groups, respectively. AFL: after flavonoid-low orange cordial group, AFR: after flavonoid-rich orange juice group.

Figure 7. Pearson correlation analysis presenting the correlation between Butyricicoccus pullicaecorum and the plasma concentrations and the amount of fecal SCFAs before and after intervention in the flavonoid-rich orange juice group. After 8 weeks of orange juice intervention, Butyricicoccus pullicaecorum significantly negatively correlated with the blood markers of human FABP2, LPS, and valeric acid and was significantly positively correlated with the amount of propionic acid. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Figure 7. Pearson correlation analysis presenting the correlation between Butyricicoccus pullicaecorum and the plasma concentrations and the amount of fecal SCFAs before and after intervention in the flavonoid-rich orange juice group. After 8 weeks of orange juice intervention, Butyricicoccus pullicaecorum significantly negatively correlated with the blood markers of human FABP2, LPS, and valeric acid and was significantly positively correlated with the amount of propionic acid. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Table 1. Baseline characteristics of the participants.

Table 1. Baseline characteristics of the participants.

VariablesFR Group
(n = 20)FL Group
(n = 20)p-ValueSex, N (%)     Male6 (30)6 (30)1.000 ‡    Female14 (70)14 (70)Age, mean ± SD, year24.70 ± 2.83023.10 ± 2.5940.070 †Residence type, N (%)    Living alone7 (35)6 (30)0.427 $    With roommate1 (5)5 (25)    With parents 9 (45)6 (30)    With parents and grandparents2 (10)1 (5)    Others1 (5)2 (10)Household income, N (%)     <1,000,000 won per month1 (5)4 (20)0.227 $    1,000,000–2,999,999 won per month6 (30)7 (35)    3,000,000–4,999,999 won per month5 (25)1 (5)    >5,000,000 won per month8 (40)8 (40)Regular physical activity, N (%)    Yes5 (25)5 (25)1.000 ‡    No15 (75)15 (75) Alcohol drinking, N (%)    None4 (20)1 (5)0.511 $    Less than once a month4 (20) 4 (20)    Once a month3 (15)6 (30)    2–4 times a month3 (15)5 (25)    2–3 times a week6 (30)4 (20)Heavy drinking frequency, N (%)    None11 (55)5 (25)0.030 $    Less than once a month 4 (20)6 (30)    Once a month 1 (5)7 (35)    Once a week 4 (20)1 (5)    Almost everyday01 (5)Smoking, N (%)    None15 (75)11 (55)0.587 $    Past smoking (no current smoking)1 (5)3 (15)    Occasionally1 (5)1 (5)    Always3 (15)5 (25)Stress, N (%)    Too much4 (20)4 (20)1.000 $    Pretty much12 (60)11 (55)    Little4 (20)5 (25)

Table 2. Anthropometric data and blood test and MDD screening results at baseline and 8 weeks after intervention.

Table 2. Anthropometric data and blood test and MDD screening results at baseline and 8 weeks after intervention.

VariablesFR Group (n = 20)p-ValueFL Group (n = 20)p-ValueΔ Group Comparison $BaselineAfter InterventionBaselineAfter InterventionMean ± SEMean ± SEWeight, kg66.33 ± 3.0967.53 ± 3.130.001 †59.70 ± 2.9160.62 ± 2.950.007 †0.512BMI, kg/m223.85 ± 0.8024.29 ± 0.800.002 †22.00 ± 0.8622.32 ± 0.870.016 †0.449Percent body fat, %31.42 ± 1.4131.07 ± 1.400.737 ‡28.48 ± 1.9727.93 ± 1.810.338 ‡0.754Skeletal muscle mass, kg 24.87 ± 1.3324.63 ± 1.430.376 ‡23.16 ± 1.0823.73 ± 1.090.285 ‡0.346SBP, mmHg119.95 ± 3.39120.00 ± 2.190.977 †113.21 ± 2.26114.95 ± 2.140.524 †0.605DBP, mmHg76.47 ± 2.4181.68 ± 1.830.064 †75.53 ± 2.7577.21 ± 2.290.475 †0.321BDNF2033.61 ± 9.162157.80 ± 19.670.000 †2123.93 ± 16.132133.75 ± 9.870.670 †0.001Serotonin, ng/mL 90.65 ± 10.98111.24 ± 14.060.268 †94.64 ± 10.6998.43 ± 14.780.846 †0.528Folate, ng/mL8.65 ± 1.249.03 ± 1.060.630 †7.50 ± 1.287.24 ± 0.840.970 ‡0.646Homocysteine, μmol/L 9.01 ± 0.928.31 ± 0.780.107 †8.73 ± 0.627.70 ± 0.510.090 †0.638hs-CRP, mg/L1.98 ± 0.691.03 ± 0.220.842 ‡0.65 ± 1.672.21 ± 1.470.395 ‡0.122Vitamin B12, pg/Ml624.70 ± 45.41607.40 ± 54.550.639 †617.45 ± 87.21609.15 ± 73.820.365 ‡0.840BDI-II26.05 ± 1.3814.10 ± 1.54<0.001 †26.55 ± 1.1817.05 ± 1.33<0.001 †0.360CES-D score34.25 ± 2.0615.90 ± 2.00<0.001 †30.30 ± 1.8218.15 ± 2.240.000 †0.110HAMD-1721.30 ± 1.118.30 ±1.29<0.001 †21.80 ± 1.0512.40 ± 1.32<0.001 †0.114