The role of inflammation and the gut microbiome in depression and anxiety

Abstract The study of the gut microbiome has increasingly revealed an important role in modulating brain function and mental health. In this review, we underscore specific pathways and mechanisms by which the gut microbiome can promote the development of mental disorders such as depression and anxiety. First, we review the involvement of the stress response and immune system activation in the development of depression and anxiety. Then, we examine germ‐free murine models used to uncover the role of the gut microbiome in developing and modulating pertinent activity in the brain and the immune system. We also document multiple pathways by which stress‐induced inflammation harms brain function and ultimately affects mental health, and review how probiotic and prebiotic treatments have shown to be beneficial. Lastly, we provide an overview of gut microbiome‐derived compounds (short‐chain fatty acids, tryptophan catabolites, microbial pattern recognition) and related mechanisms (vagal nerve activity and fecal microbiota transplants) involved in mediating the influence of the gut microbiome to mental health. Overall, a picture of the gut microbiome playing a facilitating role between stress response, inflammation, and depression, and anxiety is emerging. Future research is needed to firmly establish the microbiome's causal role, to further elucidate the mechanisms by which gut microbes influence brain function and mental health, and to possibly develop treatments that improve mental health through microbiotic targets.