Abstract

BackgroundThe role of oral and gut microbiomes in the pathogenesis of schizophrenia has recently come to light with the advancement of sequencing technology. Recent studies have shown that schizophrenia patients have different gut and oral microbiome profiles than healthy people. The interaction of oral and gut microbiota with the brain is facilitated through the gut-brain axis. Several studies have profiled the gut microbiomes in the Malaysian population, however none has investigated its relationship with etiology of schizophrenia. The aim of this preliminary study is to therefore investigate the relationship between oral and gut microbiomes in pathogenesis of schizophrenia in the Malaysian population based on the total transcriptome profiles.MethodsIn this study, 15 schizophrenia patients and 15 healthy people (control) were recruited from the three major ethnic groups in Malaysia, namely Malay, Chinese and Indian. Throat swabs and stool samples were collected and subjected to total RNA extraction. Following this, ribosomal RNA depletion and cDNA conversion were performed prior to sequencing using Illumina platform. Bioinformatic tools will be used to analyse and compare the transcriptome profiles of microbiomes from schizophrenia and healthy subjects. Brain derived neurotrophic factor, serotonin and dopamine assays will be performed using their blood samples too. The results of the bioassays will be then correlated with the transcriptome profiles to identify possible mechanisms by which microbiota could promote schizophreniaResultsThe RNA sequencing results will reveal differences in gene expression profiles between the microbiomes of schizophrenic and healthy subjects. Based on the transcriptome profiles and bioassay results, the possible pathways and mechanisms by which these microbiota can cause schizophrenia will be identified. In addition, candidate biomarkers from the oral and/or gut microbiomes for diagnosis of schizophrenia can be identified.DiscussionThe first and second generations of schizophrenia treatments mostly are based on controlling the symptoms of the disease, whereas treatment based on microbiome dysbiosis correction can tackle the underlying mechanism leading to a precise treatment of the disease.The findings from this study will enable the identification of distinct schizophrenia associated bacteria, that may help in development of new treatments and novel diagnostics for schizophrenia via microbiome-targeted therapy including probiotics and prebiotic.

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