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Cited by 8Gut microbiota and healthSchizophrenia research and treatmentMetabolomics and Mass Spectrometry Studies

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Unveiling the gut microbiota blueprint of schizophrenia: a multilevel omics approach

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Qi, DongDong, Liu, Peng, Wang, YiMeng, Tai, XuGuang, Ma, ShiFa·2024·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2024.1452604PMC PMC11461293
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Abstract

Background: Schizophrenia is a persistent incurable mental disorder and is characterized by the manifestation of negative emotions and behaviors with anxiety and depression, fear and insecurity, self-harm and social withdrawal. The intricate molecular mechanisms underlying this phenomenon remain largely elusive. Accumulating evidence points towards the gut microbiota exerting an influence on brain function via the gut-brain axis, potentially contributing to the development of schizophrenia. Therefore, the objective of this study is to delineate the gut microbial composition and metabolic profile of fecal samples from individuals with schizophrenia. Methods: Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal RNA (16S rRNA) gene sequencing were employed to analyze fecal metabolites and gut microbiota profiles in a cohort of 29 patients diagnosed with schizophrenia and 30 normal controls. The microbial composition of fecal samples was determined through the 16S rRNA gene sequencing, and microbial α-diversity and β-diversity indices were calculated. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to analyze the distribution of samples. The metabolites and gut microbiota exhibiting differential expression were identified through the application of biological variance criteria. Co-occurrence analysis of bacteria and metabolites was conducted using the spearman’s rank correlation coefficient and visualized in a circular layout with the Cytoscape software. Results: The findings of the study indicated a lack of substantial evidence supporting significant disparities in α-diversity and β-diversity between individuals with schizophrenia and normal controls. In terms of metabolomics, a discernible pattern in sample distribution between the two groups was observed. Our analysis has revealed 30 bacterial species and 45 fecal metabolites that exhibited notable differences in abundance between individuals diagnosed with schizophrenia and normal controls. These alterations in multilevel omics have led to the development of a co-expression network associated with schizophrenia. The perturbed microbial genes and fecal metabolites consistently demonstrated associations with amino acid and lipid metabolism, which play essential roles in regulating the central nervous system. Conclusion: Our results offered profound insights into the impact of imbalanced gut microbiota and metabolism on brain function in individuals with schizophrenia.

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Figure 1 Comparative analysis of gut microbiome characteristics in schizophrenia versus normal controls. (A) Depiction of bacterial α-diversity variations between schizophrenia and normal controls. (B) Significant differences observed in bacterial signatures between the two groups, as indicated by Bray-Curtis distance and PERMANOVA (P=0.001). (C) Distinct metabolic distances exhibited in schizophrenia subjects, significantly differentiated from normal controls based on Bray-Curtis distance and PERMANOVA (P=0.001).
Figure 1 Comparative analysis of gut microbiome characteristics in schizophrenia versus normal controls. (A) Depiction of bacterial α-diversity variations between schizophrenia and normal controls. (B) Significant differences observed in bacterial signatures between the two groups, as indicated by Bray-Curtis distance and PERMANOVA (P=0.001). (C) Distinct metabolic distances exhibited in schizophrenia subjects, significantly differentiated from normal controls based on Bray-Curtis distance and PERMANOVA (P=0.001).CC BY · PubMed Central
Figure 2 Discriminating bacterial species in schizophrenia and normal controls. Depiction of relative abundances of 30 bacterial species, responsible for distinguishing schizophrenia patients from normal controls. Taxonomic assignments of each species are indicated on the left.
Figure 2 Discriminating bacterial species in schizophrenia and normal controls. Depiction of relative abundances of 30 bacterial species, responsible for distinguishing schizophrenia patients from normal controls. Taxonomic assignments of each species are indicated on the left.CC BY · PubMed Central
Figure 3 Modeling analysis of schizophrenia and control groups. (A, D) Principal component analysis (PCA) representing schizophrenia and control groups in positive and negative modes, respectively. (B, E) Orthogonal partial least-squares discriminant analysis (OPLS-DA) models for schizophrenia and control groups in positive and negative modes, respectively (C, F) Permutation test analysis of schizophrenia and control groups in positive and negative modes, respectively.
Figure 3 Modeling analysis of schizophrenia and control groups. (A, D) Principal component analysis (PCA) representing schizophrenia and control groups in positive and negative modes, respectively. (B, E) Orthogonal partial least-squares discriminant analysis (OPLS-DA) models for schizophrenia and control groups in positive and negative modes, respectively (C, F) Permutation test analysis of schizophrenia and control groups in positive and negative modes, respectively.CC BY · PubMed Central
Figure 4 Discriminative fecal metabolites in schizophrenia and normal controls. Depiction of relative abundances of 45 fecal metabolites differentiating between the two groups. These metabolites were mainly involved in carbohydrate, amino acid, energy, lipid and nucleotide metabolism. Identification of discriminative metabolites is based on a LDA score exceeding 1.5.
Figure 4 Discriminative fecal metabolites in schizophrenia and normal controls. Depiction of relative abundances of 45 fecal metabolites differentiating between the two groups. These metabolites were mainly involved in carbohydrate, amino acid, energy, lipid and nucleotide metabolism. Identification of discriminative metabolites is based on a LDA score exceeding 1.5.CC BY · PubMed Central
Figure 5 Co-occurrence network of differential bacterial species and fecal metabolites in schizophrenia. A network constructed from the relative abundances of bacterial species and fecal metabolites exhibiting differential patterns in schizophrenia subjects, representing co-occurrence relationships.
Figure 5 Co-occurrence network of differential bacterial species and fecal metabolites in schizophrenia. A network constructed from the relative abundances of bacterial species and fecal metabolites exhibiting differential patterns in schizophrenia subjects, representing co-occurrence relationships.CC BY · PubMed Central
Figure 6 Enrichment analysis. Enrichment analysis of biological processes linked to differential microbial genes (A) and metabolites (B) in schizophrenia patients and normal controls.
Figure 6 Enrichment analysis. Enrichment analysis of biological processes linked to differential microbial genes (A) and metabolites (B) in schizophrenia patients and normal controls.CC BY · PubMed Central
Figure 7 Mapping of key metabolic pathways in the gut ecosystem via microbial genes and fecal metabolism. Illustration of metabolic pathways identified through the analysis of microbial genes and fecal metabolites withing the gut ecosystem. GS, Glutamine synthetase; OTC, Ornithine transcarbamylase; CSE, Cystathionine gamma-lyase; UGDH, UDP-glucose 6-dehydrogenase; UGGT, UDP-glucose glucosyltransferase.
Figure 7 Mapping of key metabolic pathways in the gut ecosystem via microbial genes and fecal metabolism. Illustration of metabolic pathways identified through the analysis of microbial genes and fecal metabolites withing the gut ecosystem. GS, Glutamine synthetase; OTC, Ornithine transcarbamylase; CSE, Cystathionine gamma-lyase; UGDH, UDP-glucose 6-dehydrogenase; UGGT, UDP-glucose glucosyltransferase.CC BY · PubMed Central

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Metadata

Authors
Qi, D., Liu, P., Wang, Y., Tai, X., & Ma, S.
Affiliations
Inner Mongolia Medical University (CN)
Corresponding author
Ma, ShiFa
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2024-09-25
Volume
15
Pages
1452604-1452604
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2024.1452604
PMC
PMC11461293
OpenAlex
W4402847199
Cited by
8
References
4
Citations by year
2026: 4 · 2025: 4
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
schizophrenia, gut microbiota, gut-brain axis, fecal metabolites, microbial diversity, amino acid metabolism, lipid metabolism

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