Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila

Area of Science:

• Neuroscience
• Microbiology
• Genomics

Background:

• The gut microbiome influences brain function via the brain-gut axis.
• Cellular and molecular mechanisms of this interaction are not fully understood.

Purpose of the Study:

• To create a comprehensive single-cell transcriptomic atlas of Drosophila melanogaster brain cells.
• To investigate the impact of the microbiome on brain cell gene expression across different ages.

Main Methods:

• Single-cell RNA sequencing of 34,427 brain cells from axenic and microbiome-associated flies.
• Cell type annotation and identification of microbiome-influenced gene signatures.
• Analysis of age-associated changes in the gut microbiome composition.

Main Results:

• Identified 56 distinct brain cell types with cell type-specific gene signatures affected by the microbiome.
• Transcriptional changes were most significant in older flies, particularly in glial cells and dopaminergic neurons.
• Differentially expressed genes were enriched in mitochondrial activity, energy metabolism, and Notch signaling pathways.
• Observed reduced Acetobacter dominance and increased microbial diversity with age, correlating with brain responses.

Conclusions:

• The microbiome exerts cell type-specific effects on brain gene expression in Drosophila.
• Age exacerbates microbiome-induced transcriptional shifts in the brain.
• These findings provide molecular insights into the gut-brain axis and its age-related changes.