Mediterranean diet consumption for 31 months increased Oscillospira gut bacteria abundance and preserved white matter volume in middle-aged female macaques, while Western diet caused brain white matter loss and insulin resistance. Higher Oscillospira levels correlated with increased short-chain fatty acids (acetate and propionate), reduced branched-chain amino acids (leucine, valine, isoleucine), and better insulin sensitivity. Crucially, Oscillospira abundance statistically mediated the diet's protective effects on both brain structure and metabolic health. This primate study provides compelling mechanistic evidence for the gut-brain axis in dietary neuroprotection. The finding is particularly significant because it identifies a specific bacterial mediator rather than just correlations between diet and brain health. However, the female-only macaque model limits generalizability to humans and males. The 31-month timeframe, equivalent to roughly 9 human years, suggests these protective effects require sustained dietary adherence. For middle-aged adults concerned about cognitive aging, this research strengthens the case for Mediterranean dietary patterns while highlighting the critical role of gut microbiome health. The identification of Oscillospira as a key mediator opens potential therapeutic avenues through targeted probiotic interventions.