Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

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Aim Schizophrenia is a serious health problem worldwide. This systematic analysis aims to quantify the burden of schizophrenia at the global, regional and national levels using the Global Burden of Disease Study 2017 (GBD 2017). Methods We collected detailed information on the number of incidence cases, disability-adjusted life years (DALYs) and age-standardised incidence rate (ASIR) and age-standardised rate of DALYs (ASDR) during 1990–2017 from GBD 2017. The estimated annual percentage changes (EAPCs) in the ASIR and in the ASDR were calculated to quantify the temporal trends in the ASIR and ASDR of schizophrenia. Results Globally there were 1.13 million (95% uncertainty interval [UI] = 1.00 to 1.28) incident schizophrenia cases and 12.66 million (95% UI = 9.48 to 15.56) DALYs due to schizophrenia in 2017. The global ASIR decreased slightly from 1990 to 2017 (EAPC = −0.124, 95% UI = −0.114 to −0.135), while the ASDR was stable. The number of incident cases, DALYs, ASIR and ASDR were higher for males than for females. The incident rate and DALYs rate were highest among those aged 20–29 and 30–54 years, respectively. ASIR and ASDR were highest in East Asia in 2017, at 19.66 (95% UI = 17.72 to 22.00) and 205.23 (95% UI = 153.13 to 253.34), respectively. In 2017, the ASIR was highest in countries with a high-moderate sociodemographic index (SDI) and the ASDR was highest in high-SDI countries. We also found that the EAPC in ASDR was negatively correlated with the ASDR in 1990 (P = 0.001, ρ = −0.23). Conclusion The global burden of schizophrenia remains large and continues to increase, thereby increasing the burden on health-care systems. The reported findings should be useful for resource allocation and health services planning for the increasing numbers of patients with schizophrenia in ageing societies.

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