Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance

Abstract

Backgroud: Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.

Aim of review: Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.

Key scientific concepts of review: The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.

Keywords: Central nervous system (CNS); Gut microbiota (GM); Microbiota-gut-brain (MGB) axis; Neuroinflammation; Short chain fatty acids (SCFAs).

Graphical abstract

Fig. 1

The molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance. CNS diseases leads to the dysbiosis of GM. Compared to the normal control, the GM dysbiosis produces more pro-inflammatory products and disrupts the microbial metabolites, such as LPS, SCFAs, and GABA. The disordered GM and metabolites not only stimulate the host to produce inflammatory factors, but also disrupt the intestinal permeability, and then lead to intestinal leakage, which affect the physiological and biochemical reactions of host through MGB axis. Lastly, the disordered GM damages the nerve cells in brain and spinal cord, and promotes the development of CNS diseases, such as AD, PD, or SCI. On the basis of in-depth analysis of GM changes with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases. In summary, there is a close relationship between CNS diseases and GM, and GM remodeling may be the effective strategy for CNS repair.

Fig. 2

Fig. The repair mechanism of GM metabolites on CNS diseases.

Fig. 3

The regulatory role of GM on development of CNS diseases.

Fig. 4

The therapeutic strategies of CNS diseases based on GM regulation.