Accumulating evidence indicates bidirectional associations between the brain and the gut microbiome with both top-down and bottom-up processes. This article describes new developments in brain-gut interactions as an introduction to a special issue of Psychosomatic Medicine, based on a joint symposium of the American Psychosomatic Society and the American Gastroenterological Association. Literature review articles indicate that several psychiatric disorders are associated with altered gut microbiota, whereas evidence linking functional gastrointestinal disorders and dysbiosis has not been firmly established. The association between dysbiosis with obesity, metabolic syndrome, and Type 2 diabetes mellitus is still inconclusive, but evidence suggests that bariatric surgery may favorably alter the gut microbial community structure. Consistent with the literature linking psychiatric disorders with dysbiosis is that life adversity during childhood and certain temperaments that develop early in life are associated with altered gut microbiota, particularly the Prevotella species. Some studies reported in this issue support the hypothesis that brain-gut interactions are adversely influenced by reduced functional activation of the hippocampus and autonomic nervous system dysregulation. The evidence for the effects of probiotics in the treatment of Clostridium difficile colitis is relatively well established, but effects on mental health and psychophysiological stress reactivity are either inconclusive or still in progress. To conceptualize brain-gut interactions, a holistic, systems-based perspective on health and disease is needed, integrating gut microbial with environmental ecology. More translational research is needed to examine the mental and physical health effects of prebiotics and probiotics, in well-phenotyped human populations with sufficiently large sample sizes.