4.5 Review

The Microbiota and Gut-Brain Axis: Contributions to the Immunopathogenesis of Schizophrenia

Journal

CURRENT PHARMACEUTICAL DESIGN
Volume 22, Issue 40, Pages 6122-6133

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612822666160906160911

Keywords

Schizophrenia; Microbiota; Immunopathogenesis; Neuroinflammation; Bacterial translocation; Leaky gut; Microbial dysbiosis; food antigens

Funding

  1. Spanish Ministry of Economy and Competitiveness
  2. Spanish Ministry of Health (ISCIII)
  3. Spanish Ministry of Health (CIBERSAM)
  4. Spanish Ministry of Health (FIS)
  5. Spanish Ministry of Health (Instituto de Investigacion Sanitaria Imas12)
  6. IUINQ
  7. Autonomous Governments of Madrid (CannabCM)
  8. Foundation (Mutua Madrilena)
  9. Foundation (Alicia Koplowitz)
  10. CIBERSAM [SAM15PINT1514]
  11. FISABIO (Spain) [UGP-14-184]

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Background: The underlying pathophysiology of schizophrenia still remains elusive. Thus, there is a pressing need to identify novel targets for the development of new interventions and elucidate related biomarkers for the identification and monitoring of potentially responsive patients. In this sense, several hypotheses involving immune/inflammatory changes and the consequent oxidative/nitrosative stress, as well as a dysregulation in the immuno-inflammatory response have come into sight. Methods: Considering the great amount of genes encoded by the microbiome and the evidences pointing to the potential role of the gut microbiota on several neurologic and psychiatric diseases, the aim of this review is to evaluate the possible role of these organisms in the immunopathogenesis of schizophrenia. To that end, we will focus not only on gut microbiota dysbiosis but also on bacterial translocation as an inductor of neuroinflammation. Results: Studies have shown that the gut microbiota may play a key role in the immunopathogenesis of schizophrenia and that essential pathways implicated in the etiopathophysiology of schizophrenia are also regulated by the microbiota-gut-brain (MGB) axis. Moreover, studies also indicate a possible role of the innate immunity through the Toll-like receptors (TLRs) and their activation by bacterial translocation, as a consequence of intestinal dysfunction, in the pathophysiology of psychotic disorders. Conclusion: This is a promising area of investigation with huge potential to offer advances in the realm of personalized medicine and accordingly, future research should examine several microbiota-targeted therapies in order to improve symptoms and to decrease the immune dysregulation seen in patients with schizophrenia.

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