The Brain-Gut-Microbiome Axis

The past decade has seen a paradigm shift in our understanding of the brain-gut axis.The exponential growth of evidence detailing the bidirectional interactions between the gut microbiome and the brain supports a comprehensive model that integrates the central nervous, gastrointestinal, and immune systems with this newly discovered organ.Data from preclinical and clinical studies have shown remarkable potential for novel treatment targets not only in functional gastrointestinal disorders but in a wide range of psychiatric and neurologic disorders, including Parkinson's disease, autism spectrum disorders, anxiety, and depression, among many others.Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis.Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms.The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression.A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit.A series of largely preclinical observations implicates alterations in braingut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders.Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.