Microbial metabolites and immune regulation: New targets for major depressive disorder

Treatments for depression and mood disorders have been singularly targeted at the brain without consideration for the context of the rest of the body. As evidence mounts for a role of autoimmunity and inflammation as risk factors and contributors to mood disorders, attention has shifted to one of the primary immunoregulatory organs in the body--the gut. Gut-brain interactions have been established and correlative links between the microbiome and mood have been examined, but with novel tools and a base of understanding, focus shifts to the mechanisms of these communications. In this review, we examine how the small molecules produced by metabolic processes of bacteria in the gut influence the host immune system. The gaps in knowledge discussed here include the under characterized diversity of small molecules crossing the gut walls, as well as the need to close the logical loop connecting the microbiome to the immune system, and the immune system to behavior and mood. As we move past the dawn of this field, more precise understanding using novel tools and techniques will help move toward a more informed and systematic process for clinically evaluating the efficacy of probiotics and bacterially derived compounds as antidepressants and mood regulators.