Short-Chain Fatty Acids in the Microbiota–Gut–Brain Axis: Role in Neurodegenerative Disorders and Viral Infections

The gut-brain axis (GBA) is the umbrella term to include all bidirectional communication between the brain and gastrointestinal (GI) tract in the mammalian body. Evidence from over two centuries describes a significant role of GI microbiome in health and disease states of the host organism. Short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate that are the physiological forms of acetic acid, butyric acid, and propionic acid respectively, are GI bacteria derived metabolites. SCFAs have been reported to influence cellular function in multiple neurodegenerative diseases (NDDs). In addition, the inflammation modulating properties of SCFAs make them suitable therapeutic candidates in neuroinflammatory conditions. This review provides a historical background of the GBA and current knowledge of the GI microbiome and role of individual SCFAs in central nervous system (CNS) disorders. Recently, a few reports have also identified the effects of GI metabolites in the case of viral infections. Among these viruses, the flaviviridae family is associated with neuroinflammation and deterioration of CNS functions. In this context, we additionally introduce SCFA based mechanisms in different viral pathogenesis to understand the former's potential as agents against flaviviral disease.