Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

Over the past few decades, extensive research has shed light on immune alterations and the significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to the integrity of both brain and intestinal barriers, may play a crucial role in the origin of peripheral and central inflammation in these pathologies. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates both the immune response and the permeability of biological barriers. Notably, S1P-based drugs, such as fingolimod and ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease of the central nervous system (CNS), and ulcerative colitis, an inflammatory condition of the colon, respectively. Although the precise mechanisms of action are still under investigation, the effectiveness of S1P-based drugs in treating these pathologies sparks a debate on extending their use in psychiatry. This comprehensive review aims to delve into the molecular mechanisms through which S1P modulates the immune system and brain/intestinal barrier functions. Furthermore, it will specifically focus on psychiatric diseases, with the primary objective of uncovering the potential of innovative therapies based on S1P signaling.