Abstract TP46: Longitudinal Effects of Diet on Cognitive Function and Fecal Metabolites in Two Genetically Diverse Wild-type Rat Strains

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Background: Modifiable lifestyle factors such as diet and genetic predisposition influence cognitive aging. The Mediterranean diet (MeDi) is associated with healthy brain aging while the Western diet (WD) is associated with cognitive impairment. Genetics may interact with dietary patterns to further impact cognitive function through the gut-brain axis. The objective of this study was to determine the effect of the MeDi on cognition and fecal metabolites relative to the WD as animals age in genetically distinct wild-type strains. Methods: Ten-week-old Male Fischer344 (F344; in-bred) and Sprague Dawley (SD; out-bred) rats were randomized to a MeDi or WD (n=8/group/strain). Y-maze and Morris water maze (MWM) were completed at 3.5, 9.5, and 15.5 months of diet to test spatial reference memory. Fecal samples for metabolomics were collected prior to behavioral assessment at 3.5 and 15.5 months. Data were analyzed using a Student’s t-test with false discovery rate of 0.1 or Two-Way Repeated Measures ANOVA, where appropriate. Results: There was no difference for Y-maze by Diet for F344 or SD rats. For MWM, there was no difference in latency to reach the platform by Diet for either strain at 3.5 or 9.5 months. However, at 15.5 months of diet, the F344 MeDi rats had a shorter latency compared to the F344 WD rats. Latency for SD rats did not differ by Diet. At 3.5 months, fecal metabolomics demonstrated 6 and 5 differing metabolites by Diet for F344 or SD rats, respectively. This increased to 202 and 139 at 15.5 months by diet for F344 or SD rats, respectively. There were 99 metabolites that overlapped by strain including an increase in deconjugated bile acids with the MeDi relative to the WD. Interestingly, the F344 had an additional 103 metabolites that were different between diets, including pathways related to glycolysis, tryptophan metabolism, and hormone production such as lower cortisol with the MeDi relative to the WD. Conclusion: Duration of diet and strain is an important factor in cognitive function and fecal metabolomics. The effect of diet on cognition was only evident at 15.5 months with the MeDi demonstrating better cognitive function relative to a WD within the F344 strain. Fecal metabolite differences increased with diet duration with greater differences found by diet in the F344 rats at 15.5 months. These metabolic and inflammatory pathway differences may be an indicator of related mechanisms contributing to the cognitive differences in F344 rats.

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