Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility [5xFAD_CD11b+_Bulk_RNA-seq]

The native microbiome influences a plethora of host processes, including neurological function. We have shown that colonization by Escherichia coli induces a distinct adaptive immune and neurogenerative disease-associated cell state in wildtype mice, suggesting increased disease susceptibility. Further, E. coli exposure in the 5xFAD mouse model results in exacerbated cognitive decline and amyloid pathology, demonstrating its sufficiency to worsen Alzheimer’s disease-relevant outcomes. Here, we performed bulk RNA-seq of CD11b+ brain myeloid cells from E. coli or vehicle treated 5xFAD mice to understand how E. coli modulates neuroimmune responses in the context of amyloid pathology. We demonstrate that E. coli exposed animals have a subtle decrease in genes associated with the disease associated microglia phenotype after 1 month of enrichment, perhaps helping to explain why these animals displayed worsened outcomes.