UCLA

Environmental factors like hypoxia and stress are important risk factors for cognitive impairment, but little is known regarding the molecular mechanisms involved. The gut microbiome is emerging as an important host-factor that mediates the effects of environmental factors on host physiologies, including brain function and behavior. As the prevalence of cognitive impairment is rapidly increasing, an active area of research is in studying how changes in the gut microbiome may impact cognitive ability in animals. Work from our laboratory has examined effects of the high fat, low carbohydrate ketogenic diet (KD) and intermittent hypoxia on the composition of the gut microbiome. Here, we highlight how the KD and hypoxia-associated microbiome impacts synaptic and transcriptomic features in the mouse hippocampus. Depletion of the microbiome in mice pre-exposed to KD and hypoxia alters global gene expression profiles in the CA3 region of the hippocampus, an area previously reported as especially vulnerable to environmental insult. Alterations in hippocampal gene expression were also observed in germ-free animals monocolonized with KD-associated bacterium, Bilophila wadsworthia relative to controls. The transcriptomic alterations correlated with alterations in synaptic structure in the hippocampus, as measured by altered number of excitatory synapses, and the expression of markers for adult hippocampal neurogenesis. Altogether, these data reveal that the gut microbiome is an important mediator of the effects of the KD and hypoxia on hippocampal physiology, which could contribute to the ability of the microbiome to modify cognitive behavior.