Alteration of Gut Microbiome in Patients With Schizophrenia Indicates Links Between Bacterial Tyrosine Biosynthesis and Cognitive Dysfunction

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  • Florence Thirion
  • Tue Haldor Hansen
  • Trine Nielsen
  • Emmanuelle Le Chatelier
  • Sébastien Fromentin
  • Magali Berland
  • Florian Plaza Oñate
  • Nicolas Pons
  • Nathalie Galleron
  • Florence Levenez
  • Lajos Markó
  • Till Birkner
  • Torben Jørgensen
  • Sofia K. Forslund
  • Ole Mors
  • Stanislav D. Ehrlich

Background: Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods: In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference were compared with gut microbiota of two age- and sex-matched control groups, composed of 132 healthy individuals and 132 individuals with metabolic syndrome. Shotgun sequencing was used to characterize fecal samples at the taxonomic and functional levels. Cognition of the patients with SCZ was evaluated using the Brief Assessment of Cognition instrument. Results: SCZ gut microbiota differed significantly from those of healthy control subjects and individuals with metabolic syndrome in terms of richness and global composition. SCZ gut microbiota were notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia, and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans, and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated with cognitive score (ρ = 0.34, q ≤ .1). Conclusions: Overall, this study shows that the gut microbiome of patients with SCZ differs greatly from that of healthy control subjects or individuals with metabolic syndrome. Cognitive function of patients with SCZ is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting that gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.

TidsskriftBiological Psychiatry Global Open Science
Udgave nummer2
Sider (fra-til)283-291
Antal sider9
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (to THH, TN, YF, HV, TH, OP). This work was supported in part by Metagenopolis (Grant No. ANR-11-DPBS-0001 [to FT, ELC, SF, MB, FPO, NP, NG, FL, SDE]). SKF was supported by the German Centre for Cardiovascular Research and by the BMBF German Ministry of Education and Research. TB was supported by DFG grant KFO339. SDE and FT had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. OP and SDE conceived the research idea. SDE, TH, and OP designed the analytical plan. HS, THH, TN, TJ, and HV recruited and examined study participants. Microbial DNA extraction and sequencing, library preparation, and sequencing quality assurance were supervised by SDE and undertaken by FL and NG. FT conducted bioinformatics analyses supported by SF, ELC, FPO, MB, and NP. FT, TB, LJ, and SKF undertook drug deconfounding of microbiome data. HS and FT wrote the draft manuscript. OP was responsible for overall supervision, edited and revised the manuscript, and is the guarantor of this study. All authors contributed to critically revising the manuscript for important intellectual content and approved the final version of the manuscript. We thank Benoit Quinquis for his help in generating the sequences and Franck Gauthier for his help in processing sequences and formatting figures and manuscript. Data are available in a public open access repository. Metagenomics reads generated in this study are available (without conditions of reuse) under the accession numbers PRJEB41217, PRJEB41786, and PRJEB41787 at the European Nucleotide Archive in the European Bioinformatics Institute ( The authors report no biomedical financial interests or potential conflicts of interest.

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© 2022 The Authors

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