Altered gut microbiota and its metabolites correlate with plasma cytokines in schizophrenia inpatients with aggression

Abstract
The pathophysiological mechanisms of aggression are manifold and they may closely interconnect. Current study aimed to determine the gut microbiota and its metabolites, and clarify their correlations with inflammation, oxidation, leaky gut and clinical profiles underlying aggression in schizophrenia (ScZ). Serum and stool specimens from ScZ inpatients with (ScZ-Ag, 25 cases) and without aggression (NScZ-Ag, 25 cases) were collected. Systemic inflammation, oxidation and leaky gut biomarkers were determined by ELISA, gut microbiota by 16S rRNA sequencing, short-chain fatty acids (SCFAs) by gas chromatography-mass spectrometry analysis and neurotransmitters by liquid chromatograph mass spectrometry analysis. Significantly higher systemic pro-inflammation, pro-oxidation and leaky gut biomarkers were observed in ScZ-Ag than NScZ-Ag group (all PPrevotella was significantly increased, while that Bacteroides, Faecalibacterium, Blautia, Bifidobacterium,Collinsella and Eubacterium_coprostanoligenes were remarkably reduced in ScZ-Ag group (all corrected PP<0.05). Finally, a few strongly positive or negative correlations among altered gut microbiota, SCFAs, systemic pro-inflammation, leaky gut, pro-oxidation and aggression severity were detected. These results demonstrate that pro-inflammation, pro-oxidation and leaky gut phenotypes relating to enteric dysbacteriosis and microbial SCFAs feature the aggression onset or severity in ScZ individuals.