A Mediterranean Diet Enhances Cognitive Function and Modulates the Gut Microbiota

OBJECTIVES: The gut-microbiome-brain axis is an underexplored mechanism that may mitigate the development of mild cognitive impairment. The objective of this study was to elucidate the effects of a human-modeled Mediterranean diet (MeDi) and Western diet (WD) on cognitive function and gut microbial composition. We hypothesized that consumption of a MeDi would improve cognitive function and modulate beneficial changes to the gut microbiota compared to the WD. METHODS: Male Sprague Dawley rats (10 weeks of age) were assigned to a MeDi (n = 10) or WD (n = 9) for 3 months. The radial arm water maze (RAWM) was used to assess aspects of short- and long-term memory using discrete error types (working and reference). Data were analyzed using a Two-Way Repeated Measures ANOVA including diet and period. Microbial composition was determined by 16S rRNA sequencing and analyzed using Linear discriminant analysis effect size (LEfSe). Simple linear regression was used to test if the significantly different genera predicted average total error scores. RESULTS: Animals consuming the MeDi committed fewer reference memory (p = 0.02), working memory incorrect (p = 0.04), and total errors (p = 0.01), and had a trend toward fewer working memory correct errors (p = 0.08) compared to the WD. MeDi gut microbiota composition was distinct (p < 0.001) and had a trend to be move diverse (Shannon, p = 0.05; Simpson, p = 0.05; Chao1, p = 0.06) compared to the WD. LEfSe analysis revealed 9 differentially abundant genera between the MeDi and WD. The MeDi had an increased abundance of 6 genera including Lachnoclostridium (p < 0.001), Candidatus Saccharimonas (p < 0.001), and Romboutsia (p = 0.01). Decreased abundances in the MeDi group included Bifidobacterium (p < 0.001) and Erysipelatoclostridium (p = 0.003). It was found that Candidatus Saccharimonas (p = 0.02, r(2) = 0.31, β = 0.007), Romboutsia (p = 0.03, r(2) = 0.25, β = 0.033), and Bifidobacterium (p = 0.01, r(2) = 0.35, β = −0.118) significantly predicted total errors. CONCLUSIONS: Relative to animals consuming the WD, the MeDi enhanced short- and long-term memory and differentially abundant genus level bacteria were predictive of memory outcomes. The MeDi may maintain cognitive function through modulation of the gut microbiota. FUNDING SOURCES: None.