Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility [snRNA-seq]

The native microbiome influences a plethora of host processes, including neurological function. However, its impacts on diverse brain cell types remains poorly understood. Here, we performed single nucleus RNA sequencing on hippocampi from wildtype, germ-free mice and reveal the microbiome-dependent transcriptional landscape across all major neural cell types. We found conserved impacts on key adaptive immune and neurodegenerative transcriptional pathways, underscoring the microbiome's contributions to disease-relevant processes. In addition, mono-colonization with Escherichia coli was found to induce a distinct adaptive immune and neurogenerative disease-associated cell state, suggesting increased disease susceptibility. Overall design: This study consists single nucleus RNA-seq data from the hippocampus of female wildtype mice with a conventional microbiome, germ-free mice without any previous exposure to microbes, and ex-germ-free mice that were mono-colonized with Escherichia coli for either 2 or 4 weeks