GSE185407
Gut microbiota-driven brain Ab amyloidosis requires Microglia
Recent evidence suggests an important role of the gut microbiome in early life on immune cell entraining. Using two independent transgenic (Tg) lines of Alzheimer's disease, we have demonstrated that life-long antibiotic (ABX)-perturbation of the gut microbiome is associated with reduced amyloid beta (Ab) plaque pathology and microglial phenotypes in male mice. Furthermore, fecal microbiota transfer (FMT) from age-matched APPPS1-21 Tg mice into long-term ABX-treated male APPPS1-21 mice partially restored amyloidosis and microgliosis, thus establishing causality. in the current studies, we planned to investigate the transcriptome profiles in APPPS1-21 mice treated with short-term abx (PND14-21) compared with vehicle treated groups in genotype-, sex- and time -dependent manner. Most importantly, we also investigated if fecal microbiota transplants from age-matched Tg male mice into short-term abx (PND14-21)-treated male mice restores brain transcriptomes to that of obsreved in vehicle-treated male mice at 9 weeks of age. Overall design: Pups receiving the antibiotic cocktail were gastric gavaged with 200ml of antibiotic cocktail (4 mg/ml kanamycin (Sigma-Aldrich K4000-5g), 0.35 mg/ml gentamicin (Sigma-Aldrich G1914-250mg), 8,500 U/ml colistin (Sigma-Aldrich C4461-1g), 2.15 mg/ml metronidazole (Sigma-Aldrich M1547-25g), and 0.45 mg/ml vancomycin (Sigma-Aldrich V2002-1g)) from post-natal day (PND) 14 to PND 21 followed by an ad libitum access to regular drinking water until the time of sacrifice at 9 weeks of age. Both WT-littermates and APPPS1-21 Tg-littermates were employed to investigate effects of early-life microbiome perturbations on the brain transcriptome profile at 9 weeks of age. Additonally, we sacrfiiced a cohort of WT and APPPS1-21Tg male pups at the age of PND24 to evaluate brain transriptome changes immediately after a completion of large-dose ABX treatments (PND14-PND21).