• Hui Chen, Lei Meng, and Liang Shen.
• Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China; Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People's Republic of China. Electronic address: 2918761601@qq.com.
• Nutrition. 2022 Jan 1; 93: 111499.

AbstractAlzheimer disease (AD) is the most common form of neurodegenerative disease in older adults and has a complicated etiology. Recently, the roles of short-chain fatty acids (SCFAs), the main metabolites generated by fermentation of dietary fiber by gut microbiota, in the pathogenesis of AD have attracted considerable interest. This study analyzed the multiple roles of SCFAs in AD pathogenesis from five aspects, including: 1) epigenetic regulation; 2) modulation of neuroinflammation; 3) maintenance of the blood-brain barrier (BBB); 4) regulation of brain metabolism; and 5) interference in amyloid protein formation. According to the currently available evidence, SCFAs, particularly butyrate, cause important biological effects that interfere with the development of AD. However, the effect of other SCFAs, such as propionate, on AD might be either beneficial or harmful to different pathways, indicating that the role of SCFAs in the pathogenesis of AD is rather complicated and warrants further investigations.Copyright © 2021 Elsevier Inc. All rights reserved.

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