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Cell Mol Gastroenterol Hepatol. 2018 Apr 12;6(2):133-148. doi: 10.1016/j.jcmgh.2018.04.003. eCollection 2018.

The Brain-Gut-Microbiome Axis.

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1
G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, Microbiome Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Abstract

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 brain-gut-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.

KEYWORDS:

2BA, secondary bile acid; 5-HT, serotonin; ANS, autonomic nervous system; ASD, autism spectrum disorder; BBB, blood-brain barrier; BGM, brain-gut-microbiome; CNS, central nervous system; ECC, enterochromaffin cell; EEC, enteroendocrine cell; FFAR, free fatty acid receptor; FGF, fibroblast growth factor; FXR, farnesoid X receptor; GF, germ-free; GI, gastrointestinal; GLP-1, glucagon-like peptide-1; GPR, G-protein–coupled receptor; IBS, irritable bowel syndrome; Intestinal Permeability; Irritable Bowel Syndrome; LPS, lipopolysaccharide; SCFA, short-chain fatty acid; SPF, specific-pathogen-free; Serotonin; Stress; TGR5, G protein-coupled bile acid receptor; Trp, tryptophan

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