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Fecal microbiota transplantation from psychiatric patients to mice - systematic review of methodologies and a call for standardization
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  • Systematic Review
  • Open access
  • Published: 12 February 2026

Fecal microbiota transplantation from psychiatric patients to mice - systematic review of methodologies and a call for standardization

  • Antonio Maria D’Onofrio1,
  • Adrian Gomez-Nguyen2,3,
  • Giovanni Camardese  ORCID: orcid.org/0000-0002-8139-92304,5,
  • Franco Scaldaferri6,7,
  • Aaron Burberry  ORCID: orcid.org/0000-0003-1552-86958 &
  • …
  • Fabio Cominelli  ORCID: orcid.org/0000-0002-1571-15482,3 

Translational Psychiatry , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Depression
  • Psychiatric disorders

Abstract

Background

Fecal microbiota transplantation (FMT) has emerged as a key tool to explore the role of the microbiome-gut-brain axis in psychiatric disorders. However, the field is hindered by significant methodological inconsistencies.

Methods

A comprehensive literature search identified 31 studies performing FMT from human patients with psychiatric conditions into rodent models.

Results

None of the 31 studies followed an identical FMT protocol. Significant heterogeneity was observed across studies in rodent model selection, including germ-free, antibiotic-pretreated, or specific pathogen-free approaches, in antibiotic regimens, timing and microbiota depletion verification, as well as in FMT donor strategy, dosage, frequency, engraftment assessment, and behavioral testing schedules.

Conclusions

This review highlights the necessity for standardized methodologies in microbiome research. Evidence-based recommendations are provided to promote reproducibility in future work. Investigators are encouraged to publish transparent and rigorous protocols, to enhance the translational potential of microbiome-gut-brain axis research.

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Data availability

All data are available in the main text or the supplementary materials.

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Funding

A.G.N. and F.C. were supported by the National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK097948. A.B. was supported by R01AG085316, 5R03AG080175-02, and Target ALS New Academic Investigators Award.

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Authors and Affiliations

  1. Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, 00168, Rome, Italy

    Antonio Maria D’Onofrio

  2. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA

    Adrian Gomez-Nguyen & Fabio Cominelli

  3. Digestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA

    Adrian Gomez-Nguyen & Fabio Cominelli

  4. Department of Life Science, Health, and Health Professions, Link Campus University, 00165, Rome, Italy

    Giovanni Camardese

  5. Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy

    Giovanni Camardese

  6. Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy

    Franco Scaldaferri

  7. Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Franco Scaldaferri

  8. Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA

    Aaron Burberry

Authors
  1. Antonio Maria D’Onofrio
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  2. Adrian Gomez-Nguyen
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  3. Giovanni Camardese
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  4. Franco Scaldaferri
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  5. Aaron Burberry
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  6. Fabio Cominelli
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Contributions

A.M.D. and A.G.N. conceptualized the study, performed the literature search, wrote the main manuscript text, and prepared figures. A.B., G.C., F.S., and F.C. provided expertise contributing to the final recommendations and edited the manuscript. All authors read and reviewed the final manuscript.

Corresponding author

Correspondence to Fabio Cominelli.

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D’Onofrio, A.M., Gomez-Nguyen, A., Camardese, G. et al. Fecal microbiota transplantation from psychiatric patients to mice - systematic review of methodologies and a call for standardization. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03847-4

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  • Received: 29 April 2025

  • Revised: 11 December 2025

  • Accepted: 20 January 2026

  • Published: 12 February 2026

  • DOI: https://doi.org/10.1038/s41398-026-03847-4

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