Schizophrenia and gut-flora related epigenetic factors

Abstract

Background: Schizophrenia (SZ) is a complex psychiatric disorder and the exact mechanisms that underpin SZ remain poorly understood despite decades of research. Genetic, epigenetic, and environmental factors are all considered to play a role. The importance of gut flora and its influence on the central nervous system has been recognized in recent years. We hypothesize that gut flora may be a converging point where environmental factors interact with epigenetic factors and contribute to SZ pathogenesis.

Aim: To summarize the current understanding of genetic and epigenetic factors and the possible involvement of gut flora in the pathogenesis of schizophrenia.

Results: We searched PubMed and Medline with a combination of the key words schizophrenia, microbiome, epigenetic factors to identify studies of genetic and epigenetic factors in the pathogenesis of schizophrenia. Numerous genes that encode key proteins in neuronal signaling pathways have been linked to SZ. Epigenetic modifications, particularly, methylation and acetylation profiles, have been found to differ in individuals that present with SZ from those that don't. Gut flora may affect epigenetic modifications by regulation of key metabolic pathway molecules, including methionine, florate, biotin, and metabolites that are acetyl group donors. Despite a lack of direct studies on the subject, it is possible that gut flora may influence genetic and epigenetic expression and thereby contribute to the pathogenesis of SZ.

Conclusion: Gut flora is sensitive to both internal and environmental stimuli and the synthesis of some key molecules that participate in the epigenetic modulation of gene expression. Therefore, it is possible that gut flora is a converging point where environmental factors interact with genetic and epigenetic factors in the pathogenesis of SZ.

Keywords: Acetylation; Epigenetic factors; Genetic factors; Gut flora; Methylation; Schizophrenia.