Alteration of gut microbiome in patients with schizophrenia indicates links between bacterial tyrosine biosynthesis and cognitive dysfunction

Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder, for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference was compared to gut microbiota of two age- and sex-matched control groups, comprising 132 healthy individuals (HC) and 132 individuals with metabolic syndrome (MS). Shotgun sequencing was used to characterize fecal samples at taxonomic and functional level. Cognition of the SCZ patients was evaluated using the Brief Assessment of Cognition instrument. SCZ gut microbiota differed significantly from those of HC and MS in terms of richness and global composition. SCZ gut microbiota was notably enriched in Flavonifractor plautii , Collinsella aerofaciens , Bilophila wadsworthia and Sellimonas intestinalis , while depleted in Faecalibacterium prausnitzii , Ruminococcus lactaris , Ruminococcus bicirculans and Veillonella rogosae . Functional potential of the gut microbiota accounted for 11% of the cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated to cognitive score (rho = 0.34, q ≤ 0.1). Overall, this study shows that the gut microbiome of SCZ patients differs greatly from that of healthy or MS controls. Cognitive function of SCZ patients is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.