AccScience Publishing / AN / Online First / DOI: 10.36922/AN025200055
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ORIGINAL RESEARCH ARTICLE

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

Lu Zeng1 ,  Xiaobin An1 ,  Wentao Xu1 ,  Jing Ma1 ,  Yang Qu1 ,  Guitian Cong1 ,  Meijie Chen1 ,  Yan Wu1 ,  Xuqiao Wang1 ,  Jinan Yang1 ,  Jing Ai1*
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1 Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, Heilongjiang, China
Advanced Neurology, 025200055 https://doi.org/10.36922/AN025200055
Received: 12 May 2025 | Revised: 27 August 2025 | Accepted: 28 August 2025 | Published online: 17 September 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

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.

Keywords
Estrogen deficiency
High-fat diet
Cognition decline
Gut microbiome
Bacteroides-Prevotella imbalance
Funding
This work was funded by the National Science and Technology Innovation 2030—Major Program of “Brain Science and Brain-Like Research” (2022ZD0211804 to J, A.).
Conflict of interest
Jing Ai is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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