Fig. 2: The E/I imbalance in the Chd8+/− mice is associated with abnormalities in both the brain and intestine.

a, b Representative traces (top), cumulative distribution plots (bottom) and bar graphs (bottom) showing the amplitude and frequency of mEPSCs (a) and mIPSCs (b) of pyramidal cells in neocortical layer V of adult mice (weeks 8–9). n = 3 mice per group. Four to six data points per mouse. n = 13 (mEPSCs/Chd8+/+), 12 (mEPSCs/Chd8+/−), 14 (mIPSCs/Chd8+/+), and 15 (mIPSCs/Chd8+/−) data points, respectively. c Levels of L-glutamate (μg/g), glutamate/GABA, and L-glutamine (μg/g) in the cerebrum of 12-week-old mice detected by the targeted metabolomics assay. n = 13 and 12 mice, respectively. d Level of L-glutamine (μg/ml) in the serum of 12-week-old mice detected by the targeted metabolomics assay. n = 12 and 10 mice, respectively. e GSEA plot showing the enrichment of the amino acid transmembrane transporter activity pathway in small intestinal cells. f UMAP plot of single-cell transcriptome profiles of intestines from 12-week-old mice. g, h Highlights of enterocyte cells expressing Slc6a19 (g) and Slc7a8 (h) in the UMAP plot (left), and comparison of the expression levels of Slc6a19 and Slc7a8 between the Chd8+/+ and Chd8+/− mice (right) (n = 4 mice). The bar plots represent the mean of abundance of Slc6a19 (top) and Slc7a8 (bottom) in enterocyte cells (n = 1527 and 3445 cells in Chd8+/+ and Chd8+/− mice, respectively). Error bars represent 95% confidence interval (CI) of mean value. i Immunofluorescence staining of SLC6A19 and SLC7A8 in the ileum of the mice at week 12. Scale bar, 20 μm. Each symbol represents one image; six to seven images per mouse. n = 17 and 22 symbols, respectively. j Western blotting analysis of SLC6A19 and SLC7A8 protein levels in the small intestine of mice at week 12 (n = 6 mice). Source data are provided as a Source Data file. Quantitative data are shown as the mean ± SEM. Statistical analysis was determined by the two-tailed Mann–Whitney test (a–d, g–j). Significance was indicated by P value (a–d, g–j). n.s. means no significant difference.