Modeling host-microbiome co-metabolism by FMT - Elucidating Gut-Brain Interactions in Bipolar Disorder

Bipolar disorder (BD), a complex mood disorder with a high suicide rate, has an unclear pathogenesis. Emerging research highlights a complex interaction between systemic and brain metabolism, altered gut microbiota, and their bidirectional communication via the gut-brain axis. This study is among the first to explore the gut microbiome's role in BD during a mixed episode using a multiomics approach to identify early microbial, metabolic, and genetic disruptions. A novel methodology was employed by modeling microbial metabolite activity through community-level interactions rather than linking individual microbial genes to functions. Using fecal microbiota transplantation (FMT) from a BD patient (YMRS = 14, HAM-D = 20) and a healthy control (YMRS = 0, HAM-D = 0), BD-associated gut dysbiosis was shown to influence behavior, gut-brain metabolomics, and endocrine gene expression in mice. Key findings included depleted Akkermansia and disrupted glutamate metabolism in BD, highlighting collective microbiome metabolic dysfunction as central to BD mechanisms.