Brain biomarker profiles vary with semi-synthetic and grain-based diets in healthy and mTBI mice

Across a range of neurological disorders, there is a growing appreciation for how the gut influences brain health, but few ways of monitoring its effects. Although nutrition influences traumatic brain injury (TBI) recovery, its influence on biomarkers-whether as an intervention or confounder-is poorly understood. Beyond specialized diets, standard rodent diets may also affect brain function. Neuron-derived extracellular vesicles (NDEVs) offer a brain-specific complement to circulating biomarkers, but their sensitivity to diet is unknown. In this study, we isolated miRNAs from NDEVs from the serum of healthy and mild TBI (mTBI) mice fed a semi-synthetic or grain-based diet. NDEV miRNAs encoded dietary differences based on injury condition, suggesting that NDEVs are sensitive to dietary changes and may be able to track diet's effect on TBI recovery. Additionally, we found that diet influenced injury biomarkers, underscoring diet as a confounding variable for NDEV miRNA biomarkers. Together, these findings highlight NDEVs as a promising tool for monitoring the effects of subtle dietary differences on brain health and the importance of diet reporting to improve study reproducibility.