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Gut microbiome variability and brain alterations in schizophrenia: A scoping review of structural and functional MRI

Federico Bottaro1, Paolo Enrico2, Giorgio Ratti1

  • 1Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Neuroscience and Biobehavioral Reviews
|May 9, 2026
PubMed
Abstract

Insights

Schizophrenia (SCZ) involves gut-brain interactions, with gut microbiome changes linked to brain alterations. These gut-brain axis findings differ between early and chronic SCZ stages.

Area of Science:

  • Neuroscience
  • Microbiology
  • Psychiatry

Background:

  • Schizophrenia (SCZ) is increasingly recognized as a multifactorial disorder with significant gut-brain interaction components.
  • Evidence indicates gut microbiome alterations and distinct structural/functional brain abnormalities in SCZ patients.
  • A comprehensive integration of gut microbiome variability and neuroimaging findings in SCZ is currently lacking.

Purpose of the Study:

  • To systematically review and integrate existing research on the association between gut microbiome variability and neuroimaging alterations in schizophrenia.
  • To examine differences in these associations between first-episode and chronic schizophrenia.

Main Methods:

  • A scoping review methodology based on the Joanna Briggs Institute guidelines and PRISMA-ScR checklist was employed.
  • Literature searches were conducted across PubMed, Scopus, and Web of Science databases.
  • Included studies focused on structural MRI (sMRI) and resting-state fMRI (fMRI) examining gut microbiome-brain associations in SCZ.

Main Results:

  • Eight studies met the inclusion criteria (one sMRI-only, one fMRI-only, six combined).
  • sMRI studies linked gut microbiome to gray matter volume in frontal, temporal, and limbic regions.
  • fMRI studies associated microbial variations with altered resting-state activity and functional connectivity in cortico-subcortical and large-scale networks.
  • Associations between gut microbiome and neuroimaging differed between early and chronic SCZ stages, indicating stage-dependent gut-brain relationships.

Conclusions:

  • The current evidence supports a significant association between gut microbiome variability and neuroimaging alterations in SCZ.
  • Emerging data suggest distinct gut-brain axis patterns in first-episode versus chronic schizophrenia patients.
  • Future longitudinal, multimodal studies are crucial for a deeper understanding of SCZ heterogeneity and improved patient stratification.
Keywords:
Brain networksFMRIFirst-episode psychosisGut microbiomeNeuroimagingSMRISchizophrenia

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