Sexually Dimorphic Effects of Dietary Vitamin D3 Supplementation on Cognition and the Gut Microbiome in Aging Rats (P14-006-19)

Increasing evidence suggests that vitamin D plays a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Here, we determined if a long-term enhanced vitamin D (VitD3, cholecalciferol) diet, higher than the standard dietary level, maintains or improves cognitive function in aging male and female rats. We also examined if the high VitD3 diet affected the gut microbiome. Beginning at 12 months of age 20 male and 20 female F344 rats were fed an AIN-93 diet containing either standard (1000 IU/kg diet) or higher (10,000 IU/kg) VitD3 for 6 months. The Morris water maze (MWM) was then used to assess learning and memory. Following the MWM, the gut microbiome from undigested chyme collected from the intestinal cecum was identified and taxonomically classified by Argonne National Laboratory using 16S rRNA sequences. ZRT Laboratory determined 25-(OH)VitD3 levels from cardiac blood. A two-way ANOVA and Tukey post-hoc was used to test for statistical significance. After 3 days of training the probe test on day 4 indicated that the higher VitD3 diet significantly reduced path length and latency (P = 0.01) to the digital platform in females but not males. On day 5 platform location was changed and animals received one day of reversal training. On day 8, three days after reversal training, the reversal probe indicated that higher dietary VitD3 improved performance in males but not females by significantly reducing path length and latency to the digital platform (P < 0.05). Analyses of the cecal microbiome content indicated that for numerous bacteria sex specific differences were present. Further, the Shannon Diversity Index of the gut microbiome indicated a significant treatment effect of higher dietary VitD3 in females (P = 0.01). The higher VitD3 diet significantly elevated 25-(OH)VitD3 blood levels. These results indicate that a high VitD3 diet may preserve cognitive acuity during aging. Further, VitD3 may have sexually dimorphic effects on memory formation. The present results replicate our previous study that a high VitD3 diet preserves cognition in aging male rats (Latimer et al. 2014). The microbiome showed sexually dimorphic differences and the high VitD3 diet appeared to affect the microbiome in females more than males. The significance of this is not clear. NIA, NIDDK.