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Cited by 506Gut microbiota and healthTryptophan and brain disordersGastrointestinal motility and disorders

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A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia

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McGuinness, A. J., Davis, J. A., Dawson, S. L., Loughman, A., Collier, F., O’Hely, M., Simpson, C. A., Green, J., Marx, W., Hair, C., Guest, G., Mohebbi, M., Berk, M., Stupart, D., Watters, D., Jacka, F. N.·2022·Molecular Psychiatry
DOI 10.1038/s41380-022-01456-3PMC PMC9126816
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Abstract

The emerging understanding of gut microbiota as ‘metabolic machinery’ influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to ‘healthy’ controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

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Crossref · 10.1038/s41380-022-01456-3

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Fig. 1 PRISMA flowchart. PRISMA flowchart and decision-making process for the inclusion of studies.
Fig. 1 PRISMA flowchart. PRISMA flowchart and decision-making process for the inclusion of studies.CC BY · PubMed Central
Fig. 2 Differences in gut microbiota α- and β-diversity in cases compared to controls across studies of MDD, BD and SZ. A Testing of differences in α-diversity across comparison groups in MDD (N = 27), BD (N = 7), and SZ (N = 18). Purple indicates no reported difference in α-diversity, dark blue indicates lower α-diversity and light blue indicates higher α-diversity. B Testing of differences in β-diversity across comparison groups in MDD (N = 18), BD (N = 6) and SZ (N = 13). Light blue indicates reported differences in β-diversity, dark blue indicates no reported difference in β-diversity.
Fig. 2 Differences in gut microbiota α- and β-diversity in cases compared to controls across studies of MDD, BD and SZ. A Testing of differences in α-diversity across comparison groups in MDD (N = 27), BD (N = 7), and SZ (N = 18). Purple indicates no reported difference in α-diversity, dark blue indicates lower α-diversity and light blue indicates higher α-diversity. B Testing of differences in β-diversity across comparison groups in MDD (N = 18), BD (N = 6) and SZ (N = 13). Light blue indicates reported differences in β-diversity, dark blue indicates no reported difference in β-diversity.CC BY · PubMed Central
Fig. 3 Bacterial genera that were commonly higher or lower in mental disorders compared to controls. Bacterial genera that were differentially abundant or discriminatory in equal to or >20% (N = 9) of the included studies that reported differences at the genus level were collated. The purple circle indicates genera that were different in SZ cases compared to controls, the blue circle indicates genera that were different in BD cases compared to controls, and the yellow circle indicates bacterial genera that were different in MDD cases compared to controls. Genera within overlapping sections indicate where differences in the abundance of that genus was a shared feature between two disorders. The centre overlap indicates genera that were commonly different in cases compared to controls across all three mental disorders. MDD Major depressive disorder, BD Bipolar disorder, SZ Schizophrenia, GABA γ-aminobutyric acid. ^ indicates butyrate-producing genera; # indicated lactic acid-producing and utilising genera; * indicates bacteria that influence glutamate and GABA metabolism. Created with BioRender.com.
Fig. 3 Bacterial genera that were commonly higher or lower in mental disorders compared to controls. Bacterial genera that were differentially abundant or discriminatory in equal to or >20% (N = 9) of the included studies that reported differences at the genus level were collated. The purple circle indicates genera that were different in SZ cases compared to controls, the blue circle indicates genera that were different in BD cases compared to controls, and the yellow circle indicates bacterial genera that were different in MDD cases compared to controls. Genera within overlapping sections indicate where differences in the abundance of that genus was a shared feature between two disorders. The centre overlap indicates genera that were commonly different in cases compared to controls across all three mental disorders. MDD Major depressive disorder, BD Bipolar disorder, SZ Schizophrenia, GABA γ-aminobutyric acid. ^ indicates butyrate-producing genera; # indicated lactic acid-producing and utilising genera; * indicates bacteria that influence glutamate and GABA metabolism. Created with BioRender.com.CC BY · PubMed Central
Fig. 4 Potential functional implications of bacterial genera implicated as different in mental disorders in this review. Bacterial genera belonging to the human gut microbiota that were commonly different or discriminatory in people with mental disorders compared to controls. The functional potential of these bacteria to (1) produce and utilise lactic acid, (2) produce butyrate, and (3) influence the metabolism of glutamate and GABA, may be mechanistic pathways through which differences in these bacteria may influence their human host and contribute to mental disorder pathophysiology. Created with BioRender.com.
Fig. 4 Potential functional implications of bacterial genera implicated as different in mental disorders in this review. Bacterial genera belonging to the human gut microbiota that were commonly different or discriminatory in people with mental disorders compared to controls. The functional potential of these bacteria to (1) produce and utilise lactic acid, (2) produce butyrate, and (3) influence the metabolism of glutamate and GABA, may be mechanistic pathways through which differences in these bacteria may influence their human host and contribute to mental disorder pathophysiology. Created with BioRender.com.CC BY · PubMed Central

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  1. Mirzayi C, Renson A, Zohra F, Elsafoury S, Kasselman L, van de Wijgert J et al. Strengthening The Organizing and Reporting of Microbiome Studies (STORMS). bioRxiv. 2020;2020.06.24.167353.

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Metadata

Authors
McGuinness, A. J., Davis, J. A., Dawson, S. L., Loughman, A., Collier, F., O’Hely, M., Simpson, C. A., Green, J., Marx, W., Hair, C., Guest, G., Mohebbi, M., Berk, M., Stupart, D., Watters, D., & Jacka, F. N.
Affiliations
  • Barwon Health (AU)
  • The University of Melbourne (AU)
  • Deakin University (AU)
Corresponding author
Jacka, F. N.
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2022-02-22
Volume
27
Issue
4
Pages
1920-1935
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-022-01456-3
PMC
PMC9126816
OpenAlex
W4213219820
Cited by
502
References
166
Citations by year
2026: 88 · 2025: 133 · 2024: 130 · 2023: 100 · 2022: 51
FWCI
10.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ResearchOnline at James Cook University (James Cook University) (submittedVersion)
  • Deakin Research Online (Deakin University) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • Pfizer
  • PA Research Foundation
  • Clifford Craig Foundation
  • Jack Brockhoff Foundation
  • Australian Government
  • European Space Agency
  • Bond University
  • Multiple Sclerosis Australia
  • Australian Academy of Science
  • Australian Rotary Health (1156072)
  • Beyond Blue
  • La Trobe University
  • Deakin University (1156072)
  • RMIT University
  • University of Melbourne (1156072)
  • Swisse Wellness
  • Servier
  • H. Lundbeck A/S
  • Epilepsy Society
  • National Institutes of Health
  • Allergan
  • Medical Research Council
  • National Health and Medical Research Council (1194982, 1156072)
  • Cancer Council Queensland
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, major depressive disorder, bipolar disorder, schizophrenia, microbial diversity, short-chain fatty acids, butyrate, lactic acid bacteria, glutamate metabolism, GABA metabolism, mental illness, microbial signatures
MeSH terms
Gastrointestinal Microbiome, Bipolar Disorder, Brain, Depressive Disorder, Major, Major Depressive Disorder, Humans, Schizophrenia

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