Diet-induced cognitive deficits: The role of dietary macronutrients, inflammation, neuroplasticity and the gut microbiota.

Obesity is an important determinant of a range of health conditions including poorer cognitive function. Despite this, remarkably little is known regarding how nutrition impacts the obesity-cognition interaction and even less research has been conducted on whether obesity is a prerequisite. My thesis aimed to rectify this.Firstly, we investigated whether weight gain, energy intake or the macronutrient composition of the diet was crucial for inducing the memory deficits. Study 1 compared the effects of 12 days exposure to a control diet supplemented with liquid sugar to an energy-dense, variable cafeteria diet. Study 2 followed the same timeline but rats were fed novel, purified diets which were matched in total energy but varied in the amount of sugar and the amount and type of fat. These studies found that hippocampal-dependent memory is particularly susceptible to dietary manipulation and that the macronutrient profile is the key.Secondly, the majority of studies have examined chronic high-energy diets and thus, there is limited data on what could be driving the deficits in such a short timeframe. We focused on brain and peripheral markers of inflammation, neuroplasticity and the gut microbiota. In Study 1, the liquid sugar diet elevated blood glucose and peripheral and hippocampal inflammation-related genes which were related to the memory deficits. Study 2 found macronutrient-specific changes in the gut microbiota which were related through Distance-based linear modelling (DistLM) to the memory deficits and inflammation-related hippocampal genes.Finally, Study 3 extended this by showing that a high dose of the probiotic VSL#3 was able to prevent the diet-induced place memory deficits but caused perirhinal-dependent object memory deficits. DistLM showed a complex relationship between hippocampal and perirhinal neuroplasticity and serotonin receptor gene expression, memory and the gut microbiota which were mediated by the diet and probiotic.These results invoke the dietary macronutrient profile rather than weight gain or energy intake in the mechanisms implicated in diet-induced memory deficits. Moreover, probiotics can be beneficial in situations of gut dysbiosis where memory deficits are evident but may be detrimental in healthy subjects