Fig. 3: Bacteroides fragilis inhibits Aβ uptake by microglia.
A 8–12-month-old male (data pooled from two independent experiments) and female wildtype (WT) mice were given weekly gavages of B. fragilis (Bf) for 2 months. Fluorescently labeled Amyloid β (Aβ)−42 was injected into the hippocampus and microglia sorted 16 h later. Created with BioRender.com. B Gating strategy for isolation of microglia from the brain and assessment of Aβ uptake. C Microglial uptake of Aβ in mice treated with Bf. p-values were calculated using a two-sided Mann–Whitney U test. D Volcano plot of differentially expressed genes in microglia isolated from Bf treated mice cohort 3) and controls and analyzed by RNA sequencing. P-values and fold changes were calculated with two-sided Wald test using the DESeq2 package in R. E Pathways altered by Bf identified by Ingenuity Pathway Analysis (IPA), including genes with a FC > ±0.2 and a p-value < 0.05. Circles are shaded according to the z-score indicating activation (red) or inhibition (blue) or no presumed direction (gray). The size of the circle corresponds to the number of genes in the pathway, F Expression of microglial genes involved in phagocytosis and protein degradation pathways indicated by the colored circle: phagocytosis (green), macropinocytosis (light blue), clathrin-mediated endocytosis (pink), protein ubiquitination (yellow), autophagy (purple), and microautophagy (dark blue). Individual replicates are shown, as well as fold change (FC) per group and significant diffferenced detected by DESeq2. Spearman R of amyloid uptake vs. normalised counts and significance p-values are shown in the right column. Male-PBS: n = 10 mice/group, Male-Bf: n = 10, Female-PBS: n = 5, Female-Bf: n = 7. Violin plots represent min, max, interquartile range and median, the dots represent mice. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.
