Early-interventional ketogenic diet enhances brain function and alters gut microbiome in healthy mice. feces metagenome

Ketogenic diet (KD) has shown a wide range of neuroprotective properties in various disorders, including epilepsy and Alzheimer’s disease. However, the underlying physiological effects of KD in healthy conditions, and whether the benefits could be maximized when KD is introduced early, remain unknown. Here we show that the early intervention of KD has significant beneficial effects in healthy mice (3-4 months of age), both in the central nervous system (CNS) and the peripheral system. In the CNS, we found that KD reduced lactate but increased alanine in hippocampus, enhanced cerebral blood flow in ventromedial hypothalamus, and improved amyloid beta transport at the blood-brain barrier. The metabolic and vascular changes were associated with reduced expression of mechanistic target of rapamycin (mTOR). In the peripheral systems, we found KD altered gut microbiota composition and diversity, which may be associated with reduced body weight and blood glucose levels observed in the study. These findings suggest that early KD intervention has systematic benefits and may protect brain functions with age. Understanding nutritional effects on CNS and peripheral systems, and their interactions, may have profound implications in human aging and age-related neurodegenerative disorders.