Imbalance of gut Bacteroides and Prevotella contributes to memory decline in ovariectomized mice fed with high-fat diet

The rates of incidence and progression of Alzheimer’s disease (AD) vary significantly among post-menopausal women. However, the mechanisms that underlie this phenomenon remain obscure. Here, we established the high-fat diet-fed ovariectomized (OVXHF) mouse model and observed significant memory deficits in this model. Using 16S rDNA sequencing, we found that OVXHF mice displayed higher biodiversity and a distinct gut microbiome composition compared with normal chow-fed mice. Functional analysis further revealed that genes associated with the iron complex transport system and ATP-binding cassette are differentially expressed in OVXHF mice. Moreover, normal fecal microbiota transplantation (FMT) successfully restored the cognitive impairments in OVXHF mice through rebalancing the gut microbiota. In particular, the Bacteroides-to-Prevotella ratio was significantly increased in OVXHF mice but rescued by FMT. Altogether, these results suggest that an imbalance between Bacteroides and Prevotella in the gut microbiota accelerates the process of cognitive dysfunction in postmenopausal women on a high-fat diet.