Neuroinflammation and memory impairment in the hippocampus following sleep loss: Amelioration by Faecalibacterium prausnitzii supplementation

Sleep deprivation (SD) is a widespread public health concern associated with cognitive dysfunction and neuroinflammation, but effective interventions are still limited. In sleep-deprived mice, a notable reduction in Faecalibacterium was observed. However, the potential of this probiotic to treat cognitive impairment caused by SD has not yet been investigated. In this study, we investigated whether supplementation with Faecalibacterium prausnitzii could alleviate cognitive dysfunction induced by SD. We demonstrated that F. prausnitzii colonization ameliorated SD-induced cognitive impairment and hippocampal neuron damage in a 72-hour SD mouse model. Metabolomics analysis revealed that differential metabolites in SD mice supplemented with F. prausnitzii were significantly enriched in pathways including the synaptic vesicle cycle and neuroactive ligand-receptor interaction, with a particularly notable decrease in γ-aminobutyric acid (GABA) levels. Transcriptomic profiling identified GABAergic and cholinergic synaptic signaling pathways as the most significantly enriched pathways differentiating SD mice with and without probiotic intervention. Integrated analysis revealed significant correlations between metabolites, including GABA, and the transcriptional profiles of genes within the GABAergic and cholinergic signaling pathways. Furthermore, pre-colonization with F. prausnitzii was found to prevent SD-induced hippocampal neuronal loss, increase the levels of key synaptic proteins (Psd-95, Syp, and Snap-25), attenuate microglial overactivation, and suppress pro-inflammatory factor expression. These results indicate that F. prausnitzii supplementation mitigates cognitive impairment, synaptic damage, and neuroinflammation caused by SD. Overall, our work provides novel insights into the role of a specific gut microbe in SD-induced neural impairment by systematically elucidating the GABA-mediated gut-brain axis mechanism through an integrated multi-omics approach.