Comparing Mediterranean and Western Diets: Cognitive and Microbiota Effects in Middle-Aged Rats.

BACKGROUND: As the global population continues to age, cognitive decline has emerged as a major area of concern. Modifiable lifestyle factors, such as diet, have been associated with the trajectory of brain aging. Dietary patterns such as the Western diet (WD) have been linked to cognitive decline, whereas a Mediterranean diet (MeDi) promotes healthy brain aging. OBJECTIVES: This study aimed to compare the effects of MeDi and WD on gut microbiota and cognitive health in middle-aged rats. Our hypothesis was that the MeDi, when introduced to middle-aged rats, would maintain cognitive health and produce a distinct gut microbiota composition relative to a WD. METHODS: Twelve-month-old male Fischer344 rats were randomly assigned to MeDi, WD, or chow (n = 10/group). After 12 wk, fecal samples were collected for 16S rRNA gene sequencing to assess microbial composition. Animals completed the following neurobehavioral assessments, including Y-maze, Morris Water Maze, and Radial Arm Water Maze. At the end of the study, the hippocampus was analyzed for gene and protein expression related to barrier integrity, glial cell activity, and neuroplasticity. RESULTS: There were trending differences in cognitive function in MeDi rats relative to WD rats. Rats exhibited distinct diet-dependent microbial phenotypes with 28 differentially abundant bacteria, including Blautia, Clostridia UCG-014, Clostridium innocuum group, Faecalibacterium, and Bifidobacterium. This was accompanied by changes in hippocampal gene expression of glial cell activity, including glial fibrillary acidic protein, ionized calcium binding protein, and triggering receptor expressed on myeloid cells 2. Blood-brain barrier integrity and neuroplasticity were maintained during the short-term dietary intervention. CONCLUSIONS: A longer diet duration may be needed to elicit robust differences in cognitive function driven by the changes in microbiota and neurobiology. This study highlights that a short-term diet introduced in middle age has trending effects on cognitive performance but significantly impacts gut microbiota composition and gene expression of biomarkers of brain health.