The gut-microbiome as a target for the treatment of schizophrenia: A systematic review and meta-analysis of randomised controlled trials of add-on strategies
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The gut-microbiome has been hypothesised as a novel potential target for intervention for schizophrenia. We tested this hypothesis with a systematic review and meta-analysis of studies investigating the efficacy and acceptability of add-on strategies known to affect the gut-microbiome for the treatment of schizophrenia. Following PRISMA guidelines, we searched from inception to August 2019 all the randomised double-blind controlled trials of add-on antibiotics, antimicrobials, pre/probiotics, and faecal transplant in schizophrenia. Primary outcomes were severity of negative symptoms and acceptability of treatment. Data were independently extracted by multiple observers and a random-mixed model was used for the analysis. Heterogeneity was assessed with the I 2 index. We identified 28 eligible trials: 21 investigated antibiotics, 4 antimicrobials (Artemisinin, Artemether, and Sodium Benzoate), 3 pre/probiotics, none faecal transplant. Results showed no effect of D-Cycloserine (10 studies; SMD, -0.16; 95% CI -0.40, 0.08; P = .20; I 2: 28.2%), Minocycline (7 studies; SMD: -0.35; 95% CI -0.70, 0.00; P = .05, I 2:77.7%), other antibiotics (2 studies), probiotics alone (1 study), and Artemisinin (1 study) on negative symptoms of schizophrenia when compared to placebo. Limited evidence suggests efficacy on negative symptoms for Sodium benzoate (2 studies; SMD, -0.63; 95%CI -1.03, -0.23; P < .001; I 2:0%), Artemether (1 study), and probiotics combined with Vitamin D (1 study) when compared to placebo. Acceptability of intervention was similar to placebo. Negative findings were mainly led by antibiotics trials, with paucity of evidence available on pre/probiotics. There is a need of expanding our knowledge on the clinical relevance of gut-microbiome-host interaction in psychosis before engaging in further trials.
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Self-citationTherapeutic Implications of the Microbial Hypothesis of Mental Illness
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Modeling psychotic disorders: Environment x environment interaction
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The Role of Neuroglia in the Development and Progression of Schizophrenia
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Prophylactic Minocycline for Delirium in Critically Ill Patients
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Association between the Oral Microbiome and Brain Resting State Connectivity in Schizophrenia
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Microglia and microbiome in schizophrenia: can immunomodulation improve symptoms?
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Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia
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Early-life cognitive effects of prebiotics and probiotics: A cross-species systematic review
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Psycho-pharmacomicrobiomics: a systematic review and meta-analysisPreprint
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Fungal Forces in Mental Health: Microbial Meddlers or Function Fixers?
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Guest Editorial: Binning bugs and beyond: The state of the schizophrenia microbiome
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Supplements Effective in the Treatment of Mental Health Conditions
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The impact of prebiotic supplementation in a triple-hit rat model of schizophrenia
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Bodziony, K., Pszonka, A., Gajewski, M., Grobelny, A., Wodziak, D., Filip, K., Dudek, J., Sochań, G., Tyniec, M., & Morshed, K. (2026) · Biuletyn Głównej Biblioteki Lekarskiej · doi:10.2478/bgbl-2026-0013
- Authors
- Minichino, A., Brondino, N., Solmi, M., Del Giovane, C., Fusar-Poli, P., Burnet, P., Cipriani, A., & Lennox, B. R.
- Affiliations
- University of Oxford (GB)
- University of Pavia (IT)
- University of Padua (IT)
- Oxford Health NHS Foundation Trust (GB)
- Corresponding author
- Minichino, Amedeo
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 234
- Pages
- 58-70
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W3013443238
- Cited by
- 50
- References
- 67
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 13 · 2021: 7 · 2020: 2
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institute for Health Research
- Oxford Cognitive Health Clinical Research Facility
- NIHR Research Professorship (RP-2017-08-ST2-006)
- NIHR Oxford and Thames Valley Applied Research Collaboration
- NIHR Oxford Health Biomedical Research Centre (BRC-1215-20005)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, schizophrenia
- MeSH terms
- Gastrointestinal Microbiome, Anti-Bacterial Agents, Humans, Psychotic Disorders, Schizophrenia, Randomized Controlled Trials as Topic, Probiotics
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