The Role of the Gut Microbiome in Bipolar Disorder and its Common Medical Comorbidities

•Gut microbiota modulates mood and behavior by impacting myelination, neurotransmitter metabolism, and immune function.•Aryl-Hydrocarbon Receptor is a pathophysiologic nexus between gut composition, neuroendocrine and immune dysfunction in BD.•Understanding gut metabolite composition will be an important next step in the process in linking microbes to pathology. Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with significant psychosocial and medical disease burden. Much difficulty has been encountered in developing novel therapeutics and objective biomarkers for clinical use in this population. In that regard, gut-microbial homeostasis appears to modulate several key pathways relevant to a variety of psychiatric, metabolic, and inflammatory disorders. Microbial impact on immune, endocrine, endocannabinoid, kynurenine, and other pathways are discussed throughout this review. Emphasis is placed on this system’s relevance to current pharmacology, diet, and comorbid illness in bipolar disorder. Despite the high level of optimism promoted in many reviews on this topic, substantial obstacles exist before any microbiome-related findings can provide meaningful clinical utility. Beyond a comprehensive overview of pathophysiology, this review hopes to highlight several key areas where progress is needed. As well, novel microbiome-associated suggestions are presented for future research.