Beneficial effect of GABA-rich fermented milk whey on nervous system and intestinal microenvironment of aging mice induced by D-galactose

This study aims to investigate the protective effect of a freeze-dried powder prepared from a fermentation milk whey containing a high-yield GABA strain (FDH-GABA) against D-galactose-induced brain injury and gut microbiota imbalances in mice by probing changes to the PI3K/AKT/mTOR signaling pathway. A prematurely aged mouse model was established by performing the subcutaneous injection of D-galactose. Subsequently, the effects of FDH-GABA on the nervous system and intestinal microenvironment of the mice were explored by measuring their antioxidant activities, anti-inflammatory state, autophagy, pathway-related target protein expression levels, and intestinal microorganisms. Compared to the D-gal group, FDH-GABA improved the levels of SOD, T-AOC, IL-10, and neurotransmitters, while it reduced the contents of MDA and TNF-α. FDH-GABA also promoted autophagy and inhibited the PI3K/AKT/mTOR signaling pathway in the brains of the aged mice. Moreover, FDH-GABA restored the diversity of their intestinal flora. Pathological observations indicated that FDH-GABA was protective against damage to the brain and intestine of D-galactose-induced aging mice. These results reveal that FDH-GABA not only improved antioxidant stress, attenuated inflammation, restored the neurotransmitter content, and protected the tissue structure of the intestine and brain, but also effectively improved their intestinal microenvironment. The ameliorative effect of FDH-GABA on premature aging showed a clear dose-response relationship, and at the same time, the changes of intestinal microorganisms showed a certain correlation with the relevant indexes of nervous system. These findings provide insight into the effect of the FDH-GABA intervention on aging, providing a novel means for alleviating detrimental neurodegenerative changes in the aging population.