Role of short chain fatty acids on astrocytes and microglia in Alzheimer's disease brain

Summary Short‐chain fatty acids (SCFAs) hold exert many nutritional benefits on both physiological and pathological processes, including host metabolism, immune modulation, and appetite control. Originating from the microbial fermentation of resistant starches and dietary fibre in the colon, SCFAs have the capability to traverse the blood–brain barrier (BBB). It is evident that SCFAs play a critical role in the development of neurodegenerative disorders such as Alzheimer's disease (AD). AD is the most common form of dementia and is characterised by the deposition of amyloid β peptides (Aβ) and tau hyperphosphorylation. SCFAs have demonstrated the potential to interfere with the protein–protein interactions required for Aβ peptides to form neurotoxic oligomers. Moreover, research indicates that the SCFAs ability to maintain endothelial integrity and interact with neuroglial cells through the BBB may assist in downregulating excessive neuroinflammatory responses to amyloid peptides. This review summarises the research on SCFAs' potential role in AD and understand their mechanism of actions on astrocytes and microglia.