Multiple roles of short-chain fatty acids in Alzheimer disease

Alzheimer 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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study highlights the significant roles of short-chain fatty acids (SCFAs) in the pathogenesis of Alzheimer's disease (AD) through epigenetic regulation, modulation of neuroinflammation, maintenance of the blood-brain barrier (BBB), regulation of brain metabolism, and interference in amyloid protein formation. Specifically, butyrate plays a key role in interfering with the development of AD, while the effects of other SCFAs like propionate may vary in different pathways, indicating the complexity of their role in AD pathogenesis.