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Cited by 139Gut microbiota and healthTryptophan and brain disordersProbiotics and Fermented Foods

Flavonoid-rich orange juice intake and altered gut microbiome in young adults with depressive symptom: a randomized controlled study

Open access
Park, Miey, Choi, Jihee, Lee, Hae-Jeung·2020·Nutrients
DOI 10.3390/nu12061815PMC PMC7353347
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

In an 8-week randomized, single-blind trial, 40 young adults with CES-D scores ≥21 consumed flavonoid-rich orange juice or a flavonoid-low orange cordial. The flavonoid-rich drink altered gut microbiome composition, especially increasing Lachnospiraceae taxa, but the paper reports no significant between-group differences in CES-D scores or serum BDNF.

Key findings

  • The study included 40 participants (16 men, 24 women; mean age 21.83 ± 2.43 years) with no dropout; 80 fecal samples were sequenced. The FR group consumed 380 mL/day containing 600 ± 5.4 mg flavonoids, while the FL group consumed 380 mL/day containing 108 ± 2.6 mg flavonoids for 8 weeks.
  • Before treatment, serum BDNF was positively correlated with the Lachnospiraceae family (Lachnospiraceae_uc and Murimonas) and negatively correlated with OCTT_g (Ruminococcaceae) in the depression-symptom group.
  • After FR treatment compared with FL treatment, the abundance of Lachnospiraceae family taxa increased, including Lachnospiraceae_uc, Eubacterium_g4, Roseburia_uc, Coprococcus_g2_uc, and Agathobacter_uc. Real-time PCR showed significantly increased Lachnospiraceae_uc and Bifidobacterium_uc in the FR group compared with before FR.
  • Post-intervention CES-D scores decreased to <20 points in both groups; adjusted multiple regression showed significant decreases in the FR group (p < 0.0001) and FL group (p < 0.001), but the discussion states there were no significant differences between FR and FL groups in CES-D scores or serum BDNF.

Methods

  • Randomized, single-blind, 8-week intervention. Forty participants aged 20–30 years were recruited from Seoul and Gyeonggi-do, with CES-D scores ≥21; exclusions included antibiotic use, family history of mental illness, diagnosed psychiatric disorders, antipsychotic medication history, or bowel disease.
  • Participants were randomly divided into FR (n = 20) and FL (n = 20) groups and consumed 190 mL twice daily before breakfast and dinner. Blood tests, 24-hour dietary recall, food frequency questionnaire, and anthropometric assessments were performed at baseline and after 8 weeks.
  • Fecal microbiota was analyzed by 16S rRNA V3–V4 sequencing on Illumina MiSeq, with real-time quantitative PCR validation. Statistical analyses included paired t-tests, two-sample t-tests or Wilcoxon signed-rank tests, Spearman’s rank correlation, and LEfSe/LDA analyses.

Limitations

  • Stated: only CES-D was used to screen depression symptoms; the number of participants with depression symptoms was small; all nutrient intake decreased in the FR group compared with the FL group except carbohydrate; and well-designed extensive studies with depressive patients are needed.
  • Stated: antibiotic and probiotic use was not permitted during the study.
  • Evident: the design was single-blind and used a flavonoid-low cordial comparator rather than an inert placebo; the discussion reports no significant between-group differences in CES-D scores or serum BDNF, limiting conclusions about clinical superiority or causality.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/nu12061815

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 70 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Blautia_uc (Lachnospiraceae) was correlated with FL treatment.

    “In our study, we found that the unidentified genus of Lachnospiraceae, Bacteroides, and Bifidobacterium was correlated with FR treatment, and that Blautia_uc (Lachnospiraceae) was correlated with FL treatment.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In our study, the unidentified genus of Lachnospiraceae, Bacteroides, and Bifidobacterium was correlated with FR treatment.

    “In our study, we found that the unidentified genus of Lachnospiraceae, Bacteroides, and Bifidobacterium was correlated with FR treatment, and that Blautia_uc (Lachnospiraceae) was correlated with FL treatment.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the FR group, 10 taxa, including Lachnospiraceae, Bacteroides, and Bifidobacterium, were more abundant than before FR.

    “In the FR group, 10 taxons, including Lachnospiraceae, Bacteroides, and Bifidobacterium, were more abundant, but only 1 taxon (Blautia_uc) increased in abundance in the FL group compared to that in the before FL group.”
    Quote in the paperSubstantial claim
  • Findingown data

    After treatment with flavonoid-rich orange juice, expression of Lachnospiraceae_uc significantly increased in the FR group compared with the before FR group, as shown by real-time PCR.

    “After groups were treated with flavonoid-rich orange juice, we observed significantly increased expression of Lachnospiraceae_uc in the FR group compared with that in the before FR group, as shown in real-time PCR (Figure 2B).”
    Quote in the paperSubstantial claim
  • Findingown data

    After adjusting for sex, age, and household income, body fat (%), homocysteine level, and hs-CRP level were significantly different (p < 0.05) between the FR and FL groups.

    “Moreover, after adjusting for sex, age, and household income, body fat (%), homocysteine level, and high-sensitivity C-reactive protein (hs-CRP) level were significantly different (p < 0.05) between the FR and FL groups (Table 1).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 42
  • Classified as probably not a substantial claim. 46

  • May combine two claims.

    Findingown data

    Relative abundances of Fusicatenibacter, PAC001043_g, and Eubacterium_g20 were positively correlated with BMI, while those of the Ruminococcaceae family (PAC001100_g and OCTT_g) and Christensenella genus were negatively correlated with BMI (p < 0.001).

    “The relative abundances of Fusicatenibacter, PAC001043_g, and Eubacterium_g20 were positively correlated with body mass index (BMI), while those of the Ruminococcaceae family (PAC001100_g and OCTT_g) and Christensenella genus were negatively correlated with BMI (p < 0.001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The serotonin level in the FR group was high but was not significantly higher than that in the FL group, and there was no significant difference between the two groups (p = 0.058).

    “The serotonin level in the FR group was high but was not significantly higher than that in the FL group, and there was no significant difference between the two groups (p = 0.058).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    LEfSe analysis showed that the Bacteroidetes phylum and Bacteroides and Subdoligranulum genera were enriched in the before FL group, while the Firmicutes phylum and Blautia, Streptococcus, and Coprococcus genera were abundant in the FL group.

    “The LEfSe analysis also showed that the Bacteroidetes phylum and Bacteroides and Subdoligranulum genera were enriched in the before FL group, while the Firmicutes phylum and Blautia, Streptococcus, and Coprococcus genera were abundant in the FL group (Figure 3A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Serum BDNF level was significantly positively correlated with the abundance of the Lachnospiraceae family (Lachnospiraceae_uc and Murimonas) and was negatively correlated with OCTT_g (Ruminococcaceae) abundance in those with depression.

    “The serum BDNF level was significantly positively correlated with the abundance of the Lachnospiraceae family (Lachnospiraceae_uc and Murimonas) and was negatively correlated with OCTT_g (Ruminococcaceae) abundance in those with depression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At the family level, Ruminococcaceae, Bacteroidaceae, and Bifidobacteriaceae were less abundant in the FL group, but Lachnospiraceae, Coriobacteriaceae, Streptococcaceae, and Lactobacillaceae were more abundant.

    “At the family level, Ruminococcaceae, Bacteroidaceae, and Bifidobacteriaceae were less abundant in the FL group, but Lachnospiraceae, Coriobacteriaceae, Streptococcaceae, and Lactobacillaceae were more abundant in this group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Real-time PCR showed that the relative abundance of Lachnospiraceae_uc and Bifidobacterium_uc was significantly increased in the FR group compared to the before FR group.

    “The results of real-time PCR showed that the relative abundance of Lachnospiraceae_uc and Bifidobacterium_uc was significantly increased in the FR group compared to that in the before FR group (Figure 5A,C).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the FL group, intake of riboflavin and niacin significantly decreased (p < 0.05), while other nutrients did not change.

    “In the FL group, the intake of riboflavin and niacin significantly decreased (p < 0.05), while that of other nutrients did not change.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At the phylum level, Firmicutes were more abundant in the gut in the before FR group than in the FR group; Bacteroidetes and Actinobacteria phyla were increasingly abundant in the FR group.

    “At the phylum level, Firmicutes were more abundant in the gut in the before FR group than in the FR group. Compared with the before FR group, the Bacteroidetes and Actinobacteria phyla were increasingly abundant in the FR group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The total flavonoid content in the orange drink was 157.9 ± 1.4 mg/100 g and that in the flavored drink was 28.4 ± 0.7 mg/100 g.

    “The total flavonoid content in the orange drink was 157.9 ± 1.4 mg/100 g and that in the flavored drink was 28.4 ± 0.7 mg/100 g (Table S3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was higher abundance of the Ruminococcaceae and Erysipelotrichaceae families in the before FR group, while the Lachnospiraceae, Bifidobacteriaceae, and Akkermansiaceae families were more abundant in the FR group.

    “There was higher abundance of the Ruminococcaceae and Erysipelotrichaceae families in the before FR group, while the Lachnospiraceae, Bifidobacteriaceae, and Akkermansiaceae families were more abundant in the FR group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the FL group, the relative abundance of Firmicutes was greater than in the before FL group, while Bacteroidetes had a lower abundance rate.

    “The relative abundance of Firmicutes was greater in the FL group than in the before FL group, while Bacteroidetes had a lower abundance rate in this group (Figure 3A).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The relative expression of Roseburia_uc in the FR group was increased compared with that in the FL group, but no significant difference was noted.

    “The relative expression of Roseburia_uc in the FR group was increased compared with that in the FL group, but no significant difference was noted (Figure 5B,E).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the FR group, Lactobacillus, Alistipes, Roseburia, unclassified Lachnospiraceae (Lachnospiraceae_uc), Akkermansia, Bifidobacterium, and Collinsella abundance rates were higher, while Faecalibacterium, Streptococcus, and Eubacterium_g23 abundance rates were lower.

    “Lactobacillus, Alistipes, Roseburia, unclassified Lachnospiraceae (Lachnospiraceae_uc), Akkermansia, Bifidobacterium, and Collinsella abundance rates were higher, while Faecalibacterium, Streptococcus, and Eubacterium_g23 abundance rates were lower in the FR group (Figure 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Homocysteine level in the FL group was significantly different and fell out of the normal range (5.0-15.0 μmol/L).

    “Homocysteine level in the FL group was significantly different and fell out of the normal range (5.0–15.0 μmol/L).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After the 8-week intervention, there were no significant differences between FR and FL groups in CES-D scores and serum BDNF levels.

    “After the 8-week intervention, we found no significant differences between FR and FL groups in the CES-D scores and the serum levels of the BDNF.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the FR group, intake of energy, protein, fat, phosphate, sodium, and vitamin B12 decreased significantly (p < 0.05), and folate and vitamin C increased significantly (p < 0.05).

    “The results of the one-day 24 h recall showed that in the FR group, only the intake of energy, protein, fat, phosphate, sodium, and vitamin B12 decreased significantly (p < 0.05), and that of folate and vitamin C increased significantly (p < 0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the FL group, the relative expression of Lachnospiraceae_uc was increased and that of Bifidobacterium_uc was decreased compared with the before FL group, but there was no significant difference.

    “However, the relative expression of Lachnospiraceae_uc was increased and that of Bifidobacterium_uc was decreased in the FL group compared with those in the before FL group, but there was no significant difference (Figure 5D,F).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Lachnospiraceae (Roseburia, Coprococcus_g2, Agathobacter, Clostridium_g24, and Eubacterium_g4), Bifidobacteriaceae (Bifidobacterium), and Bacteroidaceae (Bacteroides) were enriched in the FR group and were the major phylotypes contributing to the difference in gut microbiota composition between the before FR and FR groups.

    “Lachnospiraceae (Roseburia, Coprococcus_g2, Agathobacter, Clostridium_g24, and Eubacterium_g4), Bifidobacteriaceae (Bifidobacterium), and Bacteroidaceae (Bacteroides), which were enriched in the FR group, were the major phylotypes that contributed to the difference in the gut microbiota composition between the before FR and FR groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The numerical increase in BDNF levels in the FR group was larger than that in the FL group, but was not significantly different (p < 0.05).

    “The numerical increase in the levels in the FR group was larger than that in the FL group, but was not significantly different (p < 0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We found that a high intake of flavonoids changed the relative abundance of the gut microbiome, especially the butyrate-producing Lachnospiraceae family.

    “Although the particular association between flavonoids and depression is still unclear, we found that a high intake of flavonoids changed the relative abundance of the gut microbiome, especially the butyrate-producing Lachnospiraceae family.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed differences between the FR and FL groups are attributable to the flavonoid content of the orange juice.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The intake of all nutrients decreased in the FR group compared to the FL group except carbohydrate.

    “and the intake of all nutrients decreased in the FR group compared to those of the FL group except carbohydrate.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Dietary patterns and depression are closely related.

    “Dietary patterns and depression are closely related [4,5].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Akbaraly, 2009, Dietary pattern and depressive symptoms in middle age, Br. J. Psychiatry source

      Not checked in the free run.

    • cites [5] Li, 2017, Dietary patterns and depression risk: A meta-analysis, Psychiatry Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gut microbiomes can prevent and treat depression by increasing serotonin synthesis.

    “Additionally, it has been reported that dietary flavonoids (polyphenols) are associated with gut microbiome regulation, and these microbiomes can prevent and treat depression by increasing the synthesis of serotonin, which is a neurotransmitter in the body [16,17,18].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Dash, 2015, The gut microbiome and diet in psychiatry focus on depression, Curr. Opin. Psychiatry source

      Not checked in the free run.

    • cites [17] Clarke, 2015, Serotonin, tryptophan metabolism and the brain-gut-microbiome axis, Behav. Brain Res. source

      Not checked in the free run.

    • cites [18] Jenkins, T.A., Nguyen, J.C.D., Polglaze, K.E., and Bertrand, P.P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In an experimental animal model, probiotics may reduce pro-inflammatory immune responses and increase levels of the serotonergic precursor tryptophan, thereby ameliorating depressive symptoms.

    “An experimental animal model showed that probiotics may reduce pro-inflammatory immune responses and increase levels of the serotonergic precursor tryptophan, thereby ameliorating depressive symptoms [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Desbonnet, 2008, The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat, J. Psychiatr. Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Human gastrointestinal microbiota metabolize tryptophan into indole and subsequently 3-indolepropionic acid, a powerful neuroprotective antioxidant that scavenges free radicals.

    “Microbes and plants generally synthesize tryptophan from shikimic acid or anthranilate, and human gastrointestinal microbiota metabolize tryptophan into indole and subsequently 3-indolepropionic acid, a powerful neuroprotective antioxidant that scavenges free radicals [21,22,23].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Zhang, 2016, Microbial metabolism of dietary components to bioactive metabolites opportunities for new therapeutic interventions, Genome Med. source

      Not checked in the free run.

    • cites [22] Wikoff, 2009, Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [23] Chyan, 1999, Potent Neuroprotective Properties against the Alzheimer β-Amyloid by an Endogenous Melatonin-related Indole Structure, Indole-3-propionic Acid, J. Biol. Chem. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Depression symptoms were assessed using the CES-D, a psychiatric screening tool used to detect preexisting psychiatric disorders and used extensively in population-based studies.

    “Depression symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D), which is a psychiatric screening tool to detect preexisting psychiatric disorders and has been used extensively in population-based studies [32,33,34].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [32] Radloff, 1977, The CES-D Scale, a Self-Report Depression Scale for Research in the General Population, Appl. Psychol. Meas. source

      Not checked in the free run.

    • cites [33] Bae, 2004, Development of the Korean version of the Geriatric Depression Scale and its short form among elderly psychiatric patients, J. Psychosom. Res. source

      Not checked in the free run.

    • cites [34] Huang, 2018, Possible association of Firmicutes in the gut microbiota of patients with major depressive disorder, Neuropsychiatr. Dis. Treat. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    BDNF levels are significantly lower in patients with major depressive disorder (MDD) than in the control group.

    “BDNF levels were significantly lower in patients with major depressive disorder (MDD) than the control group, and recovery from depression after antidepressant treatment was associated with normal serum levels of BDNF in patients with MDD [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Chen, 2001, Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication, Biol. Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recovery from depression after antidepressant treatment is associated with normal serum levels of BDNF in patients with MDD.

    “BDNF levels were significantly lower in patients with major depressive disorder (MDD) than the control group, and recovery from depression after antidepressant treatment was associated with normal serum levels of BDNF in patients with MDD [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Chen, 2001, Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication, Biol. Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Probiotics, including Bifidobacteria and Lactobacilli, alleviate the immune response, decrease pathogens, and maintain the intestinal microbiota in subjects receiving antibiotic treatment.

    “Probiotics, including Bifidobacteria and Lactobacilli, also alleviate the immune response, decrease pathogens, and maintain the intestinal microbiota in subjects receiving antibiotic treatment [24,25,26].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [24] Davideau, 2016, Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis a systematic review and meta-analysis, J. Clin. Periodontol. source

      Not checked in the free run.

    • cites [25] Jafarnejad, 2016, Probiotics Reduce the Risk of Antibiotic-Associated Diarrhea in Adults (18–64 Years) but Not the Elderly (>65 Years), Nutr. Clin. Pract. source

      Not checked in the free run.

    • cites [26] Emge, 2016, Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease, Am. J. Phys. Gastrointest. Liver Phys.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary polyphenols are metabolized by microorganisms in the colon, and microbial metabolites of polyphenol, isoflavones, and lignans generally show greater permeability through the man-made gut and blood-brain barrier than their parent compound.

    “Dietary polyphenols are metabolized by microorganisms in the colon, and microbial metabolites of polyphenol, isoflavones, and lignans generally show greater permeability through the man-made gut and blood–brain barrier than their parent compound [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Johnson, S.L., Kirk, R.D., DaSilva, N.A., Ma, H., Seeram, N.P., and Bertin, M.J. (2019). Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation. Metabolites, 9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The power calculation indicated that the minimum number of participants for each group was 17.

    “The power calculation indicated that the minimum number of participants for each group was 17.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    All procedures were conducted in accordance with the Declaration of Helsinki and approved by the Gachon University Institutional Review Board.

    “All procedures were conducted in accordance with the Declaration of Helsinki [36] and approved by the Gachon University Institutional Review Board (IRB, 1044396-201803-HR-074-01).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] WMA (1964). WMA Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects, Finland World Medical Association.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study had a randomized, single-blind design.

    “The study had a randomized, single-blind design and was conducted for 8 weeks.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The study recruited 40 participants for 2 groups (20 participants each) by considering a dropout rate of 20%.

    “This study recruited 40 participants for 2 groups (20 participants each) by considering the dropout rate of 20%.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    All participants with CES-D scores ≥21 were indicated as depression in this study.

    “All participants with CES-D scores ≥21 were indicated as depression in our study [35].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Cho, 1998, Use of the Center for Epidemiologic Studies Depression (CES-D) Scale in Korea, J. Nerv. Ment. Dis. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some flavonoid metabolites are effective at traversing the blood-brain barrier.

    “The flavonoids are one of the best absorbents, and some metabolites are effective to traverse the blood–brain barrier (BBB) [51].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Williamson, 2005, Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The 8-week flavonoid intervention changed the gut microbiota taxonomic composition and diversity in the depression group.

    “Furthermore, the associations between gut microbiota and depression were investigated, and the 8-week flavonoid intervention changed the gut microbiota taxonomic composition and diversity in the depression group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Participants maintained their usual physical activity during the 8-week intervention.

  • May combine two claims.

    Premisecitation

    Polyphenols may affect the composition of the gut microbiota, and bioactive compounds in polyphenol metabolites produce clinical benefits.

    “Polyphenols may affect the composition of the gut microbiota, and bioactive compounds in polyphenol metabolites produce clinical benefits [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Fraga, 2019, The effects of polyphenols and other bioactives on human health, Food Funct. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    No separate major dietary intervention or physical activity program was offered, and participants were advised to maintain physical activities during the trial.

    “No separate major dietary intervention or physical activity program was offered. Moreover, participants were advised to maintain physical activities during the trial.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Treatment with hesperidin may have neuroprotection, attenuated oxidative damage, and restored antioxidant enzyme activities in the frontal cortex and hippocampus.

    “Moreover, treatment with hesperidin may have neuroprotection, attenuated oxidative damage, and restored antioxidant enzyme activities in the frontal cortex and hippocampus [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Menze, 2012, Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats, NeuroToxicology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Daily orange juice intake was monitored by phone and short message service, one to one by researchers.

    “Daily orange juice intake was monitored by phone and short message service (SMS), one to one by researchers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The CES-D is a widely used clinical testing tool for the presence of major depression and is known to be a good choice when sampling young adults with high levels of depressive symptoms.

    “The CES-D is a widely used clinical testing tool for the presence of major depression and is known to be a good choice when sampling young adults with high levels of depressive symptoms [49,50].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Henry, 2018, Determining the optimal clinical cutoff on the CES-D for depression in a community corrections sample, J. Affect. Disord. source

      Not checked in the free run.

    • cites [50] Umegaki, 2017, Psychometric properties of the Japanese CES–D, SDS, and PHQ–9 depression scales in university students, Psychol. Assess. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    BDNF is a neurotrophin that performs multiple functions in the central nervous system and participates in the therapeutic mechanisms of antidepressants.

    “BDNF is a neurotrophin that performs multiple functions in the central nervous system and participates in the therapeutic mechanisms of antidepressants [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Kao, 2018, Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients, Sci. Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of Clostridium was negatively associated with serum BDNF levels.

    “The prevalence of Clostridium was negatively associated with serum BDNF levels [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Jiang, 2015, Altered fecal microbiota composition in patients with major depressive disorder, Brain Behav. Immun. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The two drinks were almost identical in appearance, volume, taste, and calories, as well as in glucose, fructose, and sucrose levels, except in flavonoid content.

    “The two drinks were almost identical in appearance, volume, taste, and calories, as well as in glucose, fructose, and sucrose levels, except in the flavonoid content (Table S4).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study population was randomly divided into two groups of 20 participants each (FR and FL).

    “The volunteers were randomly divided into 2 groups of 20 participants each, the FR and FL groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In total, 80 fecal samples from 40 participants before and after the intervention were sequenced on the Illumina MiSeq sequencer.

    “In total, 80 fecal samples from 40 participants before and after the intervention were sequenced on the Illumina MiSeq sequencer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    High microbial diversity could be easily affected by age, eating habits, and other factors.

    “High microbial diversity could be easily affected by age, eating habits, and other factors [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Jang, 2019, The combination of sport and sport-specific diet is associated with characteristics of gut microbiota an observational study, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    SCFAs are involved in neuroprotection.

    “Additionally, SCFAs are involved in neurotransmitter production [75] and neuroprotection and can penetrate the blood–brain barrier [76]; therefore, they have been proposed as potential novel antidepressants [77].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Kidd, 2010, Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition, Brain Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Supplementation of Bifidobacterium increases the fecal levels of immunoglobulin A in young women.

    “Supplementation of Bifidobacterium has also been shown to increase the fecal levels of immunoglobulin A in young women [61] and to lead to changes in the levels of human immune cells [62].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Kabeerdoss, 2011, Effect of yoghurt containing Bifidobacterium lactis Bb12®on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers, Nutr. J. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The abundance of Bifidobacterium increases in the late stages of pregnancy in both women and mice, indicating the causative role of progesterone.

    “The abundance of Bifidobacterium increases in the late stages of pregnancy in both women and mice, indicating the causative role of progesterone [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Neuman, 2019, Progesterone Increases Bifidobacterium Relative Abundance during Late Pregnancy, Cell Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Supplementation of Bifidobacterium leads to changes in the levels of human immune cells.

    “Supplementation of Bifidobacterium has also been shown to increase the fecal levels of immunoglobulin A in young women [61] and to lead to changes in the levels of human immune cells [62].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Ruiz, 2017, Bifidobacteria and Their Molecular Communication with the Immune System, Front. Micro source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Ruminococcaceae family is characterized by anti-inflammatory activity and associated with a chronic low-grade inflammatory response.

    “Moreover, the Ruminococcaceae family is characterized by anti-inflammatory activity and associated with a chronic low-grade inflammatory response [68,78].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Belzer, 2012, Microbes inside—from diversity to function the case of Akkermansia, ISME J. source

      Not checked in the free run.

    • cites [78] Sokol, 2008, Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Relative abundances of bacterial genera, including Akkermansia spp., were significantly reduced in socially defeated animals, which was positively correlated with both anxiety and depression.

    “Relative abundances of bacterial genera, including Akkermansia spp., were significantly reduced in socially defeated animals, which was positively correlated with both anxiety and depression [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] McGaughey, 2019, Relative abundance of Akkermansia spp. and other bacterial phylotypes correlates with anxiety- and depressive-like behavior following social defeat in mice, Sci. Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Only CES-D was used to screen depression symptoms.

    “Only CES-D was used to screen depression symptoms, and the intake of all nutrients decreased in the FR group compared to those of the FL group except carbohydrate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Administration of prebiotics increased the relative abundance of Akkermansia during exposure to stressors.

    “However, the administration of prebiotics increased the relative abundance of Akkermansia during exposure to stressors [65,66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] Tarr, 2015, The prebiotics 3′Sialyllactose and 6′Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations Evidence for effects on the gut–brain axis, Brain Behav. Immun. source

      Not checked in the free run.

    • cites [66] Burokas, 2017, Targeting the Microbiota-Gut-Brain Axis Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice, Biol. Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polyphenol-rich cranberry extract prevented several detrimental features of the metabolic syndrome in association with the abundance of Akkermansia in the gut microbiota.

    “Moreover, polyphenol-rich cranberry extract prevented several detrimental features of the metabolic syndrome in association with the abundance of Akkermansia in the gut microbiota [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Pilon, 2016, Triggering Akkermansia with dietary polyphenols A new weapon to combat the metabolic syndrome?, Gut Microbes source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Jiang et al. (2015) reported greater microbial diversity in patients with MDD than in healthy individuals.

    “While three studies reported no significant differences in microbial diversity [57,70,71], Jiang et al. (2015) reported greater microbial diversity in patients with MDD than in healthy individuals [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Jiang, 2015, Altered fecal microbiota composition in patients with major depressive disorder, Brain Behav. Immun. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bifidobacterium influences intestinal function in infants who have received healthy breast milk.

    “Bifidobacterium is a genus that influences intestinal function in infants who have received healthy breast milk, while low but relatively stable Bifidobacterium counts are observed in adulthood [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Lackey, 2019, What’s Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study, Front. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Jiang et al. (2015) reported that the abundance of Lachnospiraceae and Ruminococcaceae decreased in patients with MDD compared with that in the control group.

    “Moreover, Jiang et al. (2015) reported that the abundance of Lachnospiraceae and Ruminococcaceae decreased in patients with MDD compared with that in the control group [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Lackey, 2019, What’s Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study, Front. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bifidobacterium bifidum colonization increases interleukin 6 (IL-6) and IL-8 cytokine levels through NF-κB activation in mice.

    “Bifidobacterium bifidum colonization increases interleukin 6 (IL-6) and IL-8 cytokine levels through NF-κB activation in mice [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Turroni, 2014, Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response, Appl. Environ. Microbiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In this study, the use of antibiotics, probiotics, and prebiotics was not allowed for assessing the microbial community.

    “In this study, the use of antibiotics, probiotics, and prebiotics was not allowed for assessing the microbial community.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Naseribafrouei et al. (2014) reported that the abundance of higher-order Bacteroidales and the Oscillibacter and Alistipes genera and lower abundance of the family Lachnospiraceae were associated with depression in the comparison of the gut microbiota between 37 patients with depression and 18 healthy controls.

    “Naseribafrouei et al. (2014) reported that the abundance of higher-order Bacteroidales and the Oscillibacter and Alistipes genera and lower abundance of the family Lachnospiraceae were associated with depression in the comparison of the gut microbiota between 37 patients with depression and 18 healthy controls [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Naseribafrouei, 2014, Correlation between the human fecal microbiota and depression, Neurogastroenterol. Motil. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Akkermansia and Bifidobacterium are well-known health-associated genera that protect against inflammation, promote immunomodulation, and promote healthy metabolic homeostasis.

    “Generally, Akkermansia and Bifidobacterium are well-known health-associated genera that protect against inflammation, promote immunomodulation, and promote healthy metabolic homeostasis [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Berk, M., Williams, L.J., Jacka, F.N., O’Neil, A., Pasco, J.A., Moylan, S., Allen, N.B., Stuart, A.L., Hayley, A.C., and Byrne, M.L. (2013). So depression is an inflammatory disease, but where does the inflammation come from?. BMC Med., 11. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Low but relatively stable Bifidobacterium counts are observed in adulthood.

    “Bifidobacterium is a genus that influences intestinal function in infants who have received healthy breast milk, while low but relatively stable Bifidobacterium counts are observed in adulthood [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Lackey, 2019, What’s Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study, Front. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    SCFAs promote the differentiation of T cells and can function as a histone deacetylase inhibitor.

    “Moreover, SCFAs promote the differentiation of T cells and can function as a histone deacetylase inhibitor [74]; therefore, SCFAs can act as a regulator of immune homeostasis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Koh, 2016, From Dietary Fiber to Host Physiology Short-Chain Fatty Acids as Key Bacterial Metabolites, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reduction in these fermentation-related bacteria precipitates a decline in SCFA production, causing intestinal barrier dysfunction.

    “Reduction in these fermentation-related bacteria precipitates a decline in SCFA production, causing intestinal barrier dysfunction [72,73].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [72] Duncan, 2007, Cultivable bacterial diversity from the human colon, Lett. Appl. Microbiol. source

      Not checked in the free run.

    • cites [73] Vince, 1990, The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system, Br. J. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The number of participants who had depression symptoms was small.

    “The number of participants who had depression symptoms was small.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Exogenous probiotic microbes, such as Bifidobacterium and Lactobacillus, reduce anxiety in human participants.

    “Furthermore, exogenous probiotic microbes, such as Bifidobacterium and Lactobacillus, have been shown to reduce anxiety in human participants [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Messaoudi, 2010, Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects, Br. J. Nutr. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Flavonoids exhibit a neuroprotective effect by falsifying inflammatory reactions and have potential therapeutic effects in terms of neuroprotection.

    “Furthermore, flavonoids exhibit a neuroprotective effect by falsifying inflammatory reactions and have potential therapeutic effects in terms of neuroprotection [80].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] Spagnuolo, 2018, Anti-inflammatory effects of flavonoids in neurodegenerative disorders, Eur. J. Med. Chem. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The abundance of Akkermansia has been suggested as a biomarker for healthy intestines and has an inverse correlation with several intestinal disorders.

    “The abundance of Akkermansia has been suggested as a biomarker for healthy intestines and has an inverse correlation with several intestinal disorders [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Belzer, 2012, Microbes inside—from diversity to function the case of Akkermansia, ISME J. source

      Not checked in the free run.

71 of 71

  • The paper relies on this without support.

    There have been limited intervention studies on the microbial metabolites of polyphenol.

    “Although previous studies have indicated that flavonoids consumed through the diet could affect gut microbiome regulation and depression, there have been limited intervention studies on the microbial metabolites of polyphenol.”

  • The paper relies on this without support.

    Studies on the effectiveness of fruits and fruit juices on the human body are still at an early stage.

    “Although fruits and fruit juices can easily supply flavonoids, such as hesperidin and narirutin, studies on their effectiveness on the human body are still at an early stage, and further studies are needed.”

  • The paper relies on this without support.

    Participants maintained their usual physical activity during the 8-week intervention.

    “Nutrient intake was not different between the two groups, and the participants maintained work-out as usual for 8 weeks.”

  • The paper relies on this without support.

    This study is the first to investigate a potential improvement effect of alterations in the microbiome due to flavonoid treatment in young adults with depressive symptoms.

    “Nonetheless, this study is meaningful as it is the first study to a potential improvement effect of alterations in the microbiome due to flavonoid treatment in young adults with depressive symptoms.”

  • The paper relies on this without support.

    The observed differences between the FR and FL groups are attributable to the flavonoid content of the orange juice.

    “we found that a high intake of flavonoids changed the relative abundance of the gut microbiome, especially the butyrate-producing Lachnospiraceae family.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a recent human intervention study, flavonoid-rich orange juice reduced depressive symptoms significantly compared with flavonoid-low orange cordial and enriched bacterial genera belonging to the Lachnospiraceae, Bifidobacteriaceae, and Bacteroidaceae families.

    “In a recent human intervention study, flavonoid-rich orange juice reduced depressive symptoms significantly compared with flavonoid-low orange cordial and enriched bacterial genera belonging to the Lachnospiraceae, Bifidobacteriaceae, and Bacteroidaceae families (167).”

    From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [167]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Roseburia result described as both nonsignificant and significant

    Major

    The results say the between-group Roseburia_uc difference was not significant; the discussion describes that difference as significant.

  • Between-group nutrient differences denied in the discussion

    Minor

    The results report significant between-group differences in folate and vitamin C intake, but the discussion says nutrient intake did not differ between groups.

  • BDNF difference called nonsignificant despite p < 0.05

    Minor

    The paper calls the difference nonsignificant while reporting a p-value below its stated significance threshold of 0.05.

  • Randomized groups listed as FR twice

    Minor

    The sequencing results section says participants were divided into two FR groups, contradicting the stated FR and FL assignment.

  • Conflicting counts of taxa increased after FL treatment

    Minor

    The results name two taxa as more abundant after FL treatment, whereas the discussion says only one taxon increased.

5 of 5

The citation lists haven’t been fetched yet

References 79 · Cited by 139

Authors
Park, M., Choi, J., & Lee, H.-J.
Affiliations
Gachon University (KR)
Corresponding author
Lee, Hae-Jeung
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2020-06-18
Volume
12
Issue
6
Pages
1815
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu12061815
PMC
PMC7353347
OpenAlex
W3036746155
Semantic Scholar
13b2b85ce91c3f21afd907971742186b7e3fc0cc
Cited by
139
References
79
Citations by year
2026: 13 · 2025: 51 · 2024: 20 · 2023: 23 · 2022: 23 · 2021: 7 · 2020: 2
FWCI
4.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
This work was supported by the National Research Foundation of Korea (NRF) and a grant funded by the Korean government (MSIT) (No. NRF-2016R1D1A1B03935435). (No. NRF-2016R1D1A1B03935435)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
flavonoids, orange juice, gut microbiota, depressive symptoms, depression, young adults, Lachnospiraceae, brain-derived neurotrophic factor, gut-brain axis, dietary intervention, fecal microbiota
MeSH terms
Fruit and Vegetable Juices, Gastrointestinal Microbiome, Adult, Depressive Disorder, Feces, Female, Flavonoids, Humans, Male, Neuropsychological Tests, Citrus sinensis, Young Adult, Seoul

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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