Microbiome Profiling Reveals Gut Dysbiosis in the Metabotropic Glutamate Receptor 5 Knockout Mouse Model of Schizophrenia
Abstract
Schizophrenia (SZ) is a psychiatric disorder that constitutes one of the top 10 global causes of disability. More recently, a potential pathogenic role for the gut microbial community (microbiota) has been highlighted, with numerous studies describing dysregulated microbial profiles in SZ patients when compared to healthy controls. However, no animal model of SZ has previously recapitulated the gut dysbiosis observed clinically. Since the metabotropic glutamate receptor 5 (mGlu5) knockout mice provide a preclinical model of SZ with strong face and predictive validity, in the present study we performed gut microbiome profiling of mGlu5 knockout (KO) and wild-type (WT) mice by 16S rRNA sequencing of bacterial genomic DNA from fecal samples, analyzing bacterial diversity and taxonomic composition, as well as gastrointestinal parameters as indicators of gut function. We found a significant genotype difference in microbial beta diversity. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota compositions, which identified a decreased relative abundance of the Erysipelotrichaceae family and Allobaculum genus in this mouse model of SZ. We also identified a signature of bacteria discriminating between the genotypes (KO and WT), consisting of the Erysipelotrichales, Bacteroidales, and Clostridiales orders and macroscopic gut differences. We thus uncovered global differential community composition in the gut microbiota profile between mGlu5 KO and…
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