Neurodegenerative diseases are a rising concern, reported in 2019 to affect approximately 50 million individuals worldwide, predicted to affect over 152 million people by 2060 (Armstrong, 2020). Neurodegenerative disorders are characterised by the progressive death of neurons, leading to atrophy of related brain regions and deterioration or loss of functions such as motor and cognitive function (Przedborski et al., 2003). Commonly known examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), dominantly inherited spinocerebellar ataxias (SCA), and prion diseases (Ross and Poirier, 2004). Each neurodegenerative disease presents different symptoms based on the brain region(s) affected (Darby et al., 2018). In addition to these direct impacts, individuals suffering from neurodegenerative diseases are more prone to debilitating mental health issues, neuropsychiatric disorders such as anxiety, depression and sleep disorder (Ben Haim and Escartin, 2022), and in some instances to changes in the gastrointestinal tract functions and gut microbiome (Peterson, 2020).

The gut microbiome refers to the dynamic ecosystem of micro-organisms and their genome in the gastrointestinal tract (Gagliani et al., 2014) and is one of the most important mediators of the bidirectional communication pathway between the central nervous system (CNS) and gastrointestinal (GI) tract, through what is known as the microbiome-gut-brain axis (Pang et al., 2023). Gut microbes are postulated to contribute to brain development, neurotransmitter regulation, microglial maturation, motor control and mood regulation (Heijtz et al., 2011; Yang et al., 2016; Chen et al., 2021). For example, studies in germ-free mice have demonstrated that neurogenesis, expression of neurotrophic factors and microglia activation are dependent on the composition and functions of the gut microbiome (Erny et al., 2015; Ogbonnaya et al., 2015; Clarke et al., 2013). Any adverse alterations to the gut microbiome composition (gut dysbiosis) and functions could lead to aberrant physiologies in the brain (Mayer et al., 2015; Cryan et al., 2019). In fact, gut dysbiosis and a reduction in the abundance of gut bacteria capable of producing SCFAs, including well-characterised SCFA like butyrate, are reported to occur within a variety of neurodegenerative diseases (Wasser et al., 2020; Den Besten et al., 2013; Blacher et al., 2019; Fricker et al., 2018). In this review, we present a summary of the known functions of butyrate, along with previously reported alterations in the levels of butyrate in specific neurodegenerative diseases. Furthermore, we discuss the potential of butyrate and alternative sources of butyrate can be used as potential treatments for these neurodegenerative disorders.