Abstract
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.
Highlights
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
We carried out shotgun sequencing on fecal samples from 90 medication-free patients and 81 healthy controls and obtained an average of 11.46 gigabases (Gb) sequence data per sample and mapped the high-quality reads onto a comprehensive reference gene catalog of 11.4 million genes[21] (Supplementary Data 4)
The gut microbiota in schizophrenic patients harbored many facultative anaerobes such as Lactobacillus fermentum, Enterococcus faecium, Alkaliphilus oremlandii, and Cronobacter sakazakii/turicensis, which are rare in a healthy gut
Summary
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. 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. Changes in the gut microbiota have been associated with neurological[11] and neurodevelopmental disorders[12,13], and recently by an independent study of schizophrenia[14]. It was recently reported that fecal transfer of the gut microbiota from patients with schizophrenia induces schizophrenia-associated behaviors in germ-free recipient mice accompanied with altered levels of glutamate, glutamine, and GABA in the hippocampus[14]. The possible role of one particular schizophrenia-enriched gut bacterial species, Streptococcus (S.) vestibularis, is explored by transplanting this bacterium into the gut of the mice with antibiotic-induced microbiota depletion and observing its effects on animal behavior and brain neurochemicals
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