Obesogenic Diet Cycling Produces Graded Effects on Cognition and Microbiota Composition in Rats

Scope: The effects of diet cycling on cognition and fecal microbiota are not well understood. Method and results: Adult male Sprague-Dawley rats were cycled between a high-fat, high-sugar "cafeteria" diet (Caf) and regular chow. The impairment in place recognition memory produced by 16 days of Caf diet was reduced by switching to chow for 11 but not 4 days. Next, rats received 16 days of Caf diet in 2, 4, 8, or 16-day cycles, each separated by 4-day chow cycles. Place recognition memory declined from baseline in all groups and was impaired in the 16- versus 2-day group. Finally, rats received 24 days of Caf diet continuously or in 3-day cycles separated by 2- or 4-day chow cycles. Any Caf diet access impaired cognition and increased adiposity relative to controls, without altering hippocampal gene expression. Place recognition and adiposity were the strongest predictors of global microbiota composition. Overall, diets with higher Caf > chow ratios produced greater spatial memory impairments and larger shifts in gut microbiota species richness and beta diversity. Conclusion: Results suggest that diet-induced cognitive deficits worsen in proportion to unhealthy diet exposure, and that shifting to a healthy chow for at least a week is required for recovery under the conditions tested here.