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. 2021 Jul 28;11(8):760. doi: 10.3390/life11080760

Table 1.

Studies on microbiota and mood disorders (MDs).

Authors and Year Type of Study Population Methods Findings
Mangiola et al., 2016 [84] Review - Selected studies on the role of gut microbiota and the use of microbiota-modulating strategies in MDs/ASD
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    Reduced (anxiety-like behaviour in GF mice after the restoration of the intestinal microbiota; Improved depression and anxiety symptoms in mice after the administration of probiotics;

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    Increased Alistipes in depressed patients; negative correlation between Faecalibacterium abundance and depression severity;

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    Modulators of gut microbiota (antibiotics, probiotics and FMT) were experienced only in experimental settings in ASD/MDs with promising results
Colpo et al., 2017 [101] Review - Selected studies on the role of inflammation and immune-based therapeutic strategies in MDs
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    Treatment with probiotics may improve behavioural symptoms (Decreased depression-like and anxiety-like behaviours) by acting on monoaminergic systems (e.g., increased serotonin availability) and/or decreasing levels of systemic inflammatory markers (decreased IL-1β, IL-6, TNF-α, microglial activation markers) in animal models and improve anxious and depressive symptoms in humans
Jiang et al., 2015 [106] Cross-sectional study 46 depressed patients (active MDD and responded MDD) and 30 HC Comparing blood samples and faecal samples using high-throughput pyrosequencing
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    Increased faecal bacterial alpha-diversity in the active-MDD, but not in the responded-MDD, compared to the HC group; differences in the composition of microbiota between groups (Increased Bacteroidetes, Proteobacteria, Actinobacteria, Enterobacteriaceae and Alistipes decreased Firmicutes, and Faecalibacterium in MDD patients); negative correlation between Faecalibacterium and severity of depressive symptoms;

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    No difference in the serum inflammatory markers, while the serum level of BDNF differed significantly between the groups
Aizawa et al., 2016 [107] Cross-sectional study 43 MDD patients and 57 HC Comparing faecal samples using bacterial rRNA-targeted reverse transcription-quantitative PCR
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    Decreased Bifidobacterium and/or Lactobacillus in patients compared to controls
Zheng et al., 2016 [108] Cross-sectional study; animal study (mice) GF and SPF Kunming mice Open-field test, Y-maze, tail suspension test, forced swimming test; 16S rRNA gene sequencing on faecal samples from MDD patients and HC; FMT
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    Depression-like behaviours in GF mice (decreased immobility time in the forced swimming test);

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    Significant differences in microbiota composition of MDD patients and HC;

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    Depression-like behaviours and disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism in GF mice after transplantation with faecal samples from MDD patients
Evans et al., 2017 [109] Cross-sectional study 115 BD patients and 64 HC Comparing faecal samples using 16S rRNA gene sequence analysis; psychometric evaluations
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    Decrease Faecalibacterium in BD;

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    Significant relationships between the fractional representation of several operational taxonomical units and the self-reported burden of disease measures within BD individuals
Flowers et al., 2017 [110] Cross-sectional study 117 BD patients (AAP-treated or non-AAP-treated) Comparing faecal samples using 16S ribosomal sequencing
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    Decreased species diversity in AAP-treated females;

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    Differences in the composition of microbiota between treatment groups (Lachnospiraceae, Akkermansia and Sutterella)
Painold et al., 2019 [112] Cross-sectional study 32 BD patients and 10 HC Comparing blood samples and faecal samples using 16S rRNA gene sequencing
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    Negative correlation between microbial alpha-diversity and illness duration;

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    Increased Actinobacteria and Coriobacteria in BD, increased Ruminococcaceae and Faecalibacterium in HC;

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    Increased Lactobacillales, Streptococcaceae and Bacilli in BD individuals with higher IL-6 levels; Increased Faecalibacterium in BD individuals with higher malondialdehyde levels; tryptophan levels associated with the family of Lactobacillaceae
Huang et al., 2019 [113] Review - 12 selected human studies
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    Decreased microbial diversity in depressed patients (Increased Actinobacteria, Enterobacteriaceae and decreased Faecalibacterium);

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    Specific gut bacteria were associated with inflammatory markers and metabolic profiles, disease severity, duration of illness, psychiatric symptoms and pharmacological treatment
Maes et al., 2008 [114] Cross-sectional study MDD patients and HC Comparing blood samples
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    Increased serum IgM and IgA against LPS of enterobacteria in MDD patients
Slyepchenko et al., 2017 [115] Narrative review - 2016 selected studies on the role of intestinal dysbiosis in the pathophysiology of MDD and somatic comorbidities
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    Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD and related medical comorbidities
Kelly et al., 2016 [116] Cross-sectional study; animal study (rats) 34 MDD patients and 33 matched HC Comparing blood, salivary and faecal samples; FMT to a microbiota-deficient rat model
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    Decreased gut microbiota richness and diversity in MDD patients (decreased Prevotellaceae) and rats after FMT from MDD patients;

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    Behavioural (anhedonia, anxiety-like behaviours) and physiological depressive features (increased CRP and intestinal transit time) and alterations in tryptophan metabolism (increased kynurenine/tryptophan ratio) in mice after faecal transplantation from MDD patients
Yang et al., 2020 [117] Cross-sectional study 156 MDD patients and 155 HC Whole-genome shotgun metagenomic and untargeted metabolomic methods
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    Increassed Bacteroides, decreased Blautia and Eubacterium in MDD patients
Patterson et al., 2019 [122] Animal study (mice) Diet-induced obese and metabolically dysfunctional mice Daily administration of GABA-producing L. brevis (L. brevis DPC6108 or L. brevis DSM32386) for 12 weeks
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    Decreased accumulation of mesenteric adipose tissue, increassed insulin secretion following glucose challenge and plasma cholesterol clearance;

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    Decreassed despair-like behaviour and basal corticosterone production during the forced swim test
Naseribafrouei et al., 2014 [125] Cross-sectional study 37 depressed patients and 18 HC Comparing faecal samples using 16S rRNA gene sequencing
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    Increassed Bacteroidales and decreased Lachnospiraceae in depressed patients;

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    Significant association between depression and one clade within the genus Oscillibacter and one clade within Alistipes
Severance et al., 2016 [127] Cross-sectional study Two cohorts totaling 947 individuals with SZ and BD, as well as HC Comparing blood samples in patients with SZ and BD, as well as HC
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    C. albicans seropositivity increased the odds for an SZ diagnosis in males, decreased cognitive scores in SZ females and correlated with decreased performance on memory modules for both disorders;

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    C. albicans IgG levels were not impacted by antipsychotic medication;

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    Elevated C. albicans levels in males with SZ and females with BD were associated with GI disturbances
Dickerson et al., 2017 [128] Review - Selected human studies on the relationship between immune alterations and microbiome in SZ and BD
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    Microbiome may affect cognition and behaviour by altering the functioning of the immune system (animal studies);

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    Evidence of increased gastrointestinal inflammation in SZ and BD based on measures of microbial translocation;

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    Increassed rate of recent antimicrobial prescription in patients with acute mania, which were associated with Increassed severity of mania symptoms
Macedo et al., 2017 [129] Narrative review - 120 selected articles on the mutual relationship between stress, depression and gut microbiota composition and antimicrobial effect of ADs and vice versa
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    MDD was associated with changes in gut permeability and microbiota composition;

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    ADs presented antimicrobial effects and, conversely, some antimicrobials presented antidepressant effects

Legend: AAP—atypical antipsychotics; Ads—antidepressants; ASD—autism spectrum disorders; BD—bipolar disorder; BDNF—brain-derived neurotrophic factor; C. albicans—Candida albicans; CRP—C reactive protein; FMT—faecal microbiota transplantation; GABA—gamma-aminobutyric acid; GF—germ-free; GI—gastrointestinal; HC—healthy controls; L. brevis—Lactobacillus brevis; LPS—lipopolysaccharide; MDD—major depressive disorder; PCR—polymerase chain reaction; SPF—specific pathogen-free; SZ—schizophrenia; TNF-α—tumor necrosis factor alpha.