The Gut Microbiome-Brain Crosstalk in Neurodegenerative Diseases

Abstract

The gut-brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the modulation of the immune system and, more directly, the production of molecules and metabolites. Small clinical and preclinical trials, in which microbial composition was manipulated using dietary changes, fecal microbiome transplantation, and probiotic supplements, have provided promising outcomes. However, results are not always consistent, and large-scale randomized control trials are lacking. Here, we give an overview of how the gut microbiome influences the GBA and could contribute to disease pathogenesis in neurodegenerative diseases.

Keywords: gut microbiome; gut–brain axis; neurodegenerative diseases.

Figure 1

The gut microbiome influences the gut–brain axis through the production of SCFAs, amyloid proteins, LPS, bile acids, and neurotransmitters. SCFAs and bile acids can enter the circulation and have been demonstrated to have an important effect on maintaining BBB homeostasis. Amyloid proteins and LPS can increase local inflammation, promoting further local and systemic protein deposition (A). On the other hand, the CNS can control epithelial permeability, gut motility, and inflammation through the autonomic nervous system and the hypothalamus–pituitary axis (B). Created with Biorender.Com.