Gut microbiota-derived short chain fatty acids act as mediators of the gut–brain axis targeting age-related neurodegenerative disorders: a narrative review

Abstract

Neurodegenerative diseases associated with aging are often accompanied by cognitive decline and gut microbiota disorder. But the impact of gut microbiota on these cognitive disturbances remains incompletely understood. Short chain fatty acids (SCFAs) are major metabolites produced by gut microbiota during the digestion of dietary fiber, serving as an energy source for gut epithelial cells and/or circulating to other organs, such as the liver and brain, through the bloodstream. SCFAs have been shown to cross the blood-brain barrier and played crucial roles in brain metabolism, with potential implications in mediating Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying mechanisms that SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, the dietary sources which determine these SCFAs production was not thoroughly evaluated yet. This comprehensive review explores the production of SCFAs by gut microbiota, their transportation through the gut–brain axis, and the potential mechanisms by which they influence age-related neurodegenerative disorders. Also, the review discusses the importance of dietary fiber sources and the challenges associated with harnessing dietary-derived SCFAs as promoters of neurological health in elderly individuals. Overall, this study suggests that gut microbiota-derived SCFAs and/or dietary fibers hold promise as potential targets and strategies for addressing age-related neurodegenerative disorders.

Keywords:

• Dietary fiber
• gut microbiota
• gut–brain-axis
• short chain fatty acids

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China, grant number 31901624; Guangdong Province Zhujiang Talent Program, grant number 2019ZT08H476; and Shenzhen Science and Technology Program, grant number 20220809161043002 and KQTD20180412181334790.