Gut Microbiota in Autophagy Regulation: New Therapeutic Perspective in Neurodegeneration

Gut microbiota and the brain are related via a complex bidirectional interconnective network. Thus, intestinal homeostasis is a crucial factor for the brain, as it can control the environment of the central nervous system and play a significant role in disease progression. The link between neuropsychological behavior or neurodegeneration and gut dysbiosis is well established, but many involved pathways remain unknown. Accumulating studies showed that metabolites derived from gut microbiota are involved in the autophagy activation of various organs, including the brain, one of the major pathways of the protein clearance system that is essential for protein aggregate clearance. On the other hand, some metabolites are evidenced to disrupt the autophagy process, which can be a modulator of neurodegeneration. However, the detailed mechanism of autophagy regulation by gut microbiota remains elusive, and little research only focused on that. Here we tried to evaluate the crosstalk between gut microbiota metabolites and impaired autophagy of the central nervous system in neurodegeneration and the key to future research regarding gut dysbiosis and compromised autophagy in neurodegenerative diseases.