Outcomes of a ketogenic dietary intervention on the gut microbiome-microglial brain axis and schizophrenia-like behaviour in mice exposed to a double-hit immune challenge

Alterations in microorganisms present in the gut are associated with various mental health disorders. It is possible that this is due to changes in microglia, the immune cells that fight infections in the brain. Microglia can consume neurons, which are the cells that talk to one another in the brain. It is possible that changes in gut microorganisms make these immune cells to eat up brain cells excessively and uncontrollably, which causes mental illness. To understand this, we will infect laboratory mice with infectious agents during pregnancy and expose them to stress during adolescence. After testing the mice for behavioral alterations, we will use imaging techniques to assess how gut microorganisms can influence microglia. We will then determine if ketogenic treatments with a clinically approved high fat and low carbohydrate diet, showing benefits on the gut and brain, can reverse harmful effects on these immune cells in the brain. Together these investigations will provide novel insights into how the gut microorganisms can affect the brain immune cells and alter behavior, resulting in mental illnesses. This research may provide new targets for the therapeutic management of mental health conditions that include schizophrenia.