Abstract

AbstractBackgroundAlterations in the gut microbiota have been observed in patients with mild cognitive impairment and Alzheimer’s disease. Dietary consumption directly modulates gut microbiota; therefore, the quality of a diet may impact cognitive function and susceptibility to dementia. We hypothesized that consumption of the nutrient dense Mediterranean diet (MeDi) would improve cognitive function through beneficial changes to the gut microbiota as compared to the diet primarily consumed by Americans, the Western diet (WD).MethodTen‐week‐old Sprague Dawley male rats were assigned a MeDi (n = 10) or WD (n = 9). After three months, Morris water maze (MWM) was used to assess spatial reference memory cognition. MWM data were analyzed with two‐way RM ANOVA. Fecal samples were collected prior to the MWM. Microbial composition was determined by 16S rRNA sequencing, and analyses included Mann‐Whitney with false discovery rate.ResultThe MeDi group also spent significantly more time in the target quadrant during probe testing (p = 0.03) and was quicker to reach the platform on reversal testing (p = 0.004), indicative of improved cognitive flexibility. Microbiota α‐diversity indices, Shannon (p = 0.053), Simpson (p = 0.054), and Chao1 (p = 0.056), had a trend to be increased in the MeDi. Microbiota β‐diversity was dissimilar between diets (p<0.001). At the phylum level, Actinobacteria decreased and Patescibacteria increased with consumption of the MeDi as compared to the WD. Actinobacteria relative abundance correlated with MWM time in target quadrant (r = ‐0.58, p = 0.009). Further, relative abundance of Actinobacteria and Patescibacteria correlated with MWM reversal distance to reach platform (Actinobacteria, r = 0.77, p = 0.0001; Patescibacteria, r = ‐0.59, p = 0.007).ConclusionThe MeDi maintained long‐term spatial memory, as measured by the MWM, compared to the WD. Additionally, diet‐modulated gut microbiota at the phylum level and these changes were correlated with cognitive function. Modulation of the gut microbiota through a neuroprotective diet, such as the MeDi, may serve as a method to improve cognitive function.

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