Goat Milk Fat Globule Membrane Supplementation Ameliorates Alzheimer Disease Cognitive Impairment by Modulating the Gut Microbiota.

Research has found Alzheimer disease (AD) is accompanied by cognitive dysfunction and gut microbiota imbalance. Goat milk fat globule membrane (GMFGM) derived from goat milk, is a membrane primarily composed of proteins and polar lipids that regulates the gut microbiota. However, its role in AD remains unclear. Therefore, we examined the neuroprotective effects of GMFGM in 5xFAD mice. Supplementation with GMFGM (400 mg/kg bw, 8 weeks) improved cognitive performance, reduced brain Aβ deposition, alleviated neuroinflammation, and upregulated neurotrophic factors. Moreover, GMFGM preserved gut barrier integrity, lowered serum LPS levels, and reshaped gut microbiota composition, decreasing Alistipes, Dorea formicigenerans, and Duncaniella dubosii while increasing Stenotrophomonas. Further fecal microbiota transplantation validated the mechanism by which GMFGM ameliorates AD cognitive impairment by modulating the gut microbiota. These results indicate that GMFGM may rescue cognition by modulating the gut microbiota, alleviating gut damage, reducing LPS levels, and consequently inhibiting neuroinflammatory.