Abstract
Schizophrenia is a debilitating psychiatric disorder, leading to both physical and social morbidity. Despite its importance, the etiology of schizophrenia remains poorly understood. Furthermore, its mainstream treatments fail to address all aspects of the disorder and are associated with significant side-effects. Recently, there has been growing interest in the relationship between the gut microbiome and mental health, including in schizophrenia. In this article, we review the existing evidence implicating dysbiosis in schizophrenia and discuss how the presumed dysbiosis could fit within known hypotheses of its pathogenesis, focusing on inflammation, tryptophan metabolites, and BDNF levels. We also evaluate the clinical potential of manipulating the gut microbiome with probiotics and prebiotics as adjunctive treatments in schizophrenia, based on existing clinical and pre-clinical studies. Overall, the current data showing microbiome alterations in schizophrenia are highly discrepant and insufficient to conclude whether microbiome changes are associated with increased risk of the disorder, or are simply the result of external factors or treatment. Despite some encouraging results of pro/prebiotic supplementation, there is also inconclusive evidence for their efficacy in schizophrenia. Thus, further research and more clinical trials are needed to test the validity of manipulating the gut microbiome to improve the treatment of this disorder.
Highlights
Schizophrenia is a debilitating psychiatric disorder, characterized by positive symptoms, and negative symptoms [1]
The gut microbiome has been implicated in psychiatric disorders, and is well-described for depression, with dysbiosis suggested in clinical studies [10] and fecal transplants from depressed patients to germ-free rats shown to induce depressive-like behaviors [11]
Study design (Microbial richness/diversity) aStudy group: 81 high-risk subjects, 19 ultra-high risk subjects, 69 healthy controls; all participants were 13–30 year-old Han Chinese individuals Exclusion criteria: GI and endocrine diseases, serious organ disorders, history of psychiatric disorders and corresponding treatment, use of medication within previous 3 months Experimental method: 16S rRNA gene sequencing from fecal samples bStudy group: 64 schizophrenic patients, and 53 healthy controls; 18–65 year-old Han Chinese individuals Exclusion criteria: chronic disease in the last 3 months, use of medication within the last 6 months Experimental method: 16S rRNA gene sequencing from fecal samples
Summary
Schizophrenia is a debilitating psychiatric disorder, characterized by positive symptoms (delusions, hallucinations, aberrant flow of thoughts), and negative symptoms (apathy, withdrawal, slowness) [1] It affects ∼21 million people worldwide, and causes significant physical and social morbidity [2, 3]. Accurate definition of a healthy baseline microbiome is near impossible to establish, so it is unclear what qualitative and quantitative changes in the microbiome composition constitute functionally significant deviations from the “norm,” what thresholds should be set when assessing the importance of relative deviations from controls, and whether these should be different for various populations Bearing these limitations in mind, we take the term dysbiosis to mean microbiome profiles which are significantly different from controls and which could have functional significance in pathological processes if conclusively proven. The therapeutic potential of pre/probiotics in schizophrenia will be discussed
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