Brain modulation by the gut microbiota: From disease to therapy

BACKGROUND: The gut microbiota (GM) and brain are strongly associated, which significantly affects neuronal development and disorders. GM-derived metabolites modulate neuronal function and influence many cascades in age-related neurodegenerative disorders (NDDs). Because of the dual role of GM in neuroprotection and neurodegeneration, understanding the balance between beneficial and harmful bacteria is crucial for applying this approach to clinical therapies. AIM OF THE REVIEW: This review briefly discusses the role of the gut-brain relationship in promoting brain and cognitive function. Although a healthy gut environment is helpful for brain function, gut dysbiosis can disrupt the brain's environment and create a vicious cycle of degenerative cascades. The ways in which the GM population can affect brain function and the development of neurodegeneration are also discussed. In the treatment and management of NDDs, the beneficial effects of methods targeting GM populations and their derivatives, including probiotics, prebiotics, and fecal microbial transplantation (FMT) are also highlighted. KEY SCIENTIFIC CONCEPT OF THE REVIEW: In this review, we aimed to provide a deeper understanding of the mechanisms of the gut microbe-brain relationship and their twin roles in neurodegeneration progression and therapeutic applications. Here, we attempted to highlight the different pathways connecting the brain and gut, together with the role of GM in neuroprotection and neuronal development. Furthermore, potential roles of GM metabolites in the pathogenesis of brain disorders and in strategies for its treatment are also investigated. By analyzing existing in vitro, in vivo and clinical studies, this review attempts to identify new and promising therapeutic strategies for central nervous system (CNS) disorders. As the connection between the gut microbe-brain relationship and responses to NDD treatments is less studied, this review will provide new insights into the global mechanisms of GM modulation in disease progression, and identify potential future perspectives for developing new therapies to treat NDDs.