A single-cell transcriptomic atlas of all cell types in the entire 5xFAD mouse brain in response to dietary inulin supplementation

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that becomes a major threat to the aging population. Due to lack of effective therapy, preventive treatments are important strategies to limit AD onset and progression, of which dietary patterns have been implicated as a key influencer. Diet with high fiber content is known to have beneficial effects on cognitive decline in AD. However, a global survey on brain cell dynamics in response to high fiber intake at single-cell resolution is still missing. Here, we show that dietary inulin supplementation synergized with AD progression to specifically increase the abundance of Akkermansia muciniphila in gut microbiome of the 5x Familial AD (FAD) mice. By performing single-nucleus RNA sequencing on different regions of the whole brain with three independent biological replicates, we reveal region-specific changes in the proportion of neuron, astrocyte and granule cell subpopulations upon inulin supplementation in 5xFAD mice. Intriguingly, such dietary change only marginally alleviated astrogliosis and microgliosis, without affecting the amyloid-beta plaque burden. These results provide a comprehensive overview on the transcriptomic changes in individual cells of the entire mouse brain in response to high fiber intake, which provides a resourceful foundation for future mechanistic studies on related topics