Branched-chain amino acids and gut microbiota: coregulation and impact on neurological function via the gut-brain axis

Diseases that cause neurological dysfunction, such as Parkinson's disease (PD), Alzheimer's disease (AD), and maple syrup urine disease (MSUD), among others, are characterized by complex and multifaceted etiologies. There is growing evidence that branched-chain amino acids (BCAAs), regulated by the gut microbiota, play a critical role in the development of the central nervous system (CNS) disorders. This review focuses on the potential role of branched-chain amino acid metabolism in regulating brain function and gut microbiota. First, we summarize the current understanding of BCAAs, encompassing their biochemical metabolism, function, and systemic metabolic mechanisms. Subsequently, we delve into the mechanisms through which the gut microbiota regulates branched-chain amino acid metabolism, along with its mechanistic insights and recent evidence of its impact on neurological disorders. Finally, we discuss future research directions and challenges regarding gut BCAAs metabolism as a potential treatment for brain and gastrointestinal dysfunction.