Metabonomic Research In Multiple Regions Of Schizophrenia Microbiota Recipient Mice

Purpose: Schizophrenia is a debilitating psychiatric and highly prevalent disorder characterized by molecular and anatomical abnormalities of multiple brain regions.Our recent study showed that dysbiosis of the gut microbiota contributes to the onset of schizophrenia-relevant behaviors through moudlation of the hippocampal glutamate-glutamine-GABA cycle,but the underlying mechanisms remain largely unknown.Further,it is necessary to explore the metabolic changes in other important brain regions.Methods: This study aimed to investigate how gut microbiota shapes metabolic signatures in multiple brain regions of schizophrenia microbiota recipient mice.Gas chromatography-mass spectrometry(GC-MS)and liquid chromatography-mass spectrometry(LC-MS)were used to compare the metabolic signatures in the cortex,cerebellum and striatum of schizophrenia microbiota and healthy microbiota recipient mice.Annotation and enrichment analysis was further conducted to uncover the crucial metabolic pathways related to schizophrenia-relevant behaviors.Results: We found that the metabolic phenotypes of these three regions were substantially different in schizophrenia microbiota recipient mice from those in healthy microbiota recipient mice.In total,we identified differential metabolites(cortex:149,cerebellum:137,striatum:197)that could discriminate the two groups in the three brain regions.These differential metabolites were mainly involved in glycerophospholipid and fatty acyl metabolism.Moreover,we found four of fatty acyl metabolites that were consistently altered in the three brain regions.Conclusion: Taken together,our study suggests that alterations of glycerophospholipid and fatty acyl metabolism are implicated in the onset of schizophrenia-relevant behaviors,which may provide a new understanding of the etiology of schizophrenia.