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Meta-Analysis
. 2021 Dec 1;78(12):1343-1354.
doi: 10.1001/jamapsychiatry.2021.2573.

Perturbations in Gut Microbiota Composition in Psychiatric Disorders: A Review and Meta-analysis

Viktoriya L Nikolova  1 , Megan R B Smith  2 , Lindsay J Hall  3   4   5 , Anthony J Cleare  1   6   7 , James M Stone  1   8 , Allan H Young  1   6   7
Affiliations
Meta-Analysis

Perturbations in Gut Microbiota Composition in Psychiatric Disorders: A Review and Meta-analysis

Viktoriya L Nikolova et al. JAMA Psychiatry. .

Erratum in

  • Add Open Access.
    [No authors listed] [No authors listed] JAMA Psychiatry. 2022 Jan 1;79(1):87. doi: 10.1001/jamapsychiatry.2021.3277. JAMA Psychiatry. 2022. PMID: 34730785 Free PMC article. No abstract available.
  • Error in Author Name.
    [No authors listed] [No authors listed] JAMA Psychiatry. 2022 Dec 1;79(12):1241. doi: 10.1001/jamapsychiatry.2022.3295. JAMA Psychiatry. 2022. PMID: 36197674 Free PMC article. No abstract available.

Abstract

Importance: Evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions.

Objective: To conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison.

Data sources: Cochrane Library, PubMed, PsycINFO, and Embase were searched up to February 2, 2021, for systematic reviews, meta-analyses, and original evidence.

Study selection: A total of 59 case-control studies evaluating diversity or abundance of gut microbes in adult populations with major depressive disorder, bipolar disorder, psychosis and schizophrenia, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, or attention-deficit/hyperactivity disorder were included.

Data extraction and synthesis: Between-group comparisons of relative abundance of gut microbes and beta diversity indices were extracted and summarized qualitatively. Random-effects meta-analyses on standardized mean difference (SMD) were performed for alpha diversity indices.

Main outcomes and measures: Alpha and beta diversity and relative abundance of gut microbes.

Results: A total of 34 studies provided data and were included in alpha diversity meta-analyses (n = 1519 patients, n = 1429 control participants). Significant decrease in microbial richness in patients compared with control participants were found (observed species SMD = -0.26; 95% CI, -0.47 to -0.06; Chao1 SMD = -0.5; 95% CI, -0.79 to -0.21); however, this was consistently decreased only in bipolar disorder when individual diagnoses were examined. There was a small decrease in phylogenetic diversity (SMD = -0.24; 95% CI, -0.47 to -0.001) and no significant differences in Shannon and Simpson indices. Differences in beta diversity were consistently observed only for major depressive disorder and psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found. Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched. The confounding associations of region and medication were also evaluated.

Conclusions and relevance: This systematic review and meta-analysis found that gut microbiota perturbations were associated with a transdiagnostic pattern with a depletion of certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacteria in patients with depression, bipolar disorder, schizophrenia, and anxiety.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cleare reported grants from Protexin Probiotics International (industrial partner of the Medical Research Council studentship that Ms Nikolova is funded by) outside the submitted work; received honoraria for educational activities from Lundbeck and Janssen in the last 3 years; honoraria for consulting from Allergan, Livanova, and Janssen; and sponsorship for conference attendance from Janssen. Ms Nikolova reported personal fees from Janssen. Dr Stone reported grants from Protexin Probiotics International, personal fees from Janssen, and grants from Takeda outside the submitted work. Dr Young has received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Company, and Sunovion; honoraria for consulting from Allergan, Livanova, Lundbeck, Sunovion, and Janssen; and research grants from Janssen, Compass, and Protexin Probiotics International in the last 3 years. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Forest Plots of Alpha Diversity Richness Estimators in the Gut Microbiota of Patients With Psychiatric Disorders Compared With Healthy Controls
ADHD indicates attention-deficit/hyperactivity disorder; FEP, first episode psychosis; MDD, major depressive disorder; NA, not applicable; OCD, obsessive compulsive disorder; PI, prediction interval; PTSD, posttraumatic stress disorder; SMD, standardized mean difference.
Figure 2.
Figure 2.. Forest Plots of Alpha Diversity in the Gut Microbiota of Patients With Psychiatric Disorders Compared With Healthy Controls
ADHD indicates attention-deficit/hyperactivity disorder; FEP, first episode psychosis; MDD, major depressive disorder; NA, not applicable; OCD, obsessive compulsive disorder; PI, prediction interval; PTSD, posttraumatic stress disorder; SMD, standardized mean difference.
Figure 3.
Figure 3.. Changes in Relative Abundance of Microbial Taxa Reported by at Least 2 Studies From a Diagnostic Category
Gray cells indicate not examined, not reported, or not replicated. aMost replicated findings are indicated here, all of which have been reported by more than 1 research group. Number of studies: anorexia nervosa (AN), 10; bipolar disorder (BD), 9; major depressive disorder (MDD), 21; anxiety (ANX), 2; psychosis and schizophrenia (SCZ), 11.
See this image and copyright information in PMC

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