GRID2 aberration leads to disturbance in neuroactive ligand-receptor interactions via changes to the species richness and composition of gut microbes

To explore the association between phenotype and the gut microbiome following damage to the GRID2 gene. Ten wild-type (WT) mice and 11 GRID2 knockout heterozygous mice (GRID2(±)) of a similar age and weight were randomly selected. Fresh feces were collected from both groups of mice under specified pathogen-free (SPF) conditions. The bacterial genomes were extracted from the feces, the 16S rRNA genes were sequenced, and the data were analyzed to determine clustering, diversity, abundance, LEfSe, and functional differences. Differential expression and enrichment analyses of the RNA-seq and protein levels of the GRID2 gene were also performed using data in the GENE database and the new version of the Human Protein Atlas portal (www.proteinatlas.org). The diversity analysis showed differences in species composition between the two groups at different levels. At phylum level, compared with the WT group, the distribution was more bacteriophages but showed a lower content of Tenericutes in the GRID2(±) group. At the order level, compared with the WT group, a higher content of Actinomycetales and Bacteriophages were found in the GRID2(±) group. The species difference analysis showed that 17 species, including E. faecalis and Paracoccus spp., showed differences in content between the two groups. LEfSe analysis showed that the abundance of Clostridiaceae, Allobaculum, and other groups decreased in the GRID2(±) group compared with the WT group, while Mycoplasma, Sphingomonas, and Alphaproteobacteria increased in abundance. Functional analysis revealed eight differential functions between the WT and GRID2(±) group (P