The Brain-Gut-Microbiotal Axis: A framework for understanding functional GI illness and their therapeutic interventions

Functional gastrointestinal disorders (FGIDs), characterized by chronic abdominal complaints without a structural or biochemical cause, are common diseases that are frequently encountered by specialists in internal medicine. Collectively, irritable bowel syndrome (IBS) and functional dyspepsia are estimated to affect up to 22% of the population, and are often associated with additional somatic and pain complaints, all without an obvious structural source [[1]Ford AC Marwaha A Sood R Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis.Gut. 2015; 64 (Epub 2014/08/26PubMed PMID: 25147201): 1049-1057https://doi.org/10.1136/gutjnl-2014-307843Crossref PubMed Scopus (199) Google Scholar,[2]Hungin AP Whorwell PJ Tack J Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects.Aliment Pharmacol Ther. 2003; 17 (Epub 2003/03/19. PubMed PMID: 12641512): 643-650Crossref PubMed Scopus (588) Google Scholar. An appreciation of the current understanding of the mechanistic basis for these disorders is key to developing treatment goals and optimization of patient management strategies. In recent years, the brain-gut axis increasingly has been recognized as a central factor in the experience of functional abdominal pain disorders, including the most recent Rome IV guidelines which identify FGIDs as disorders of gut-brain interaction [[3]Drossman DA Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction.Gastroenterology. 2016; 150 (Epub 2016/05/06PubMed PMID: 27147121): 1257-1261https://doi.org/10.1053/j.gastro.2016.03.035Abstract Full Text Full Text PDF PubMed Scopus (500) Google Scholar]. The brain-gut axis (BGA), simply defined, is a complex network of bidirectional communication between the central and enteric nervous systems. This axis broadly includes all the systems involved with communication between the GI tract and central nervous system (CNS), with principle inputs into this network occurring between the CNS, enteric nervous system (ENS), and autonomic nervous systems (ANS), but also includes interfaces with numerous other factors, including endocrine hormones and immune effector cells as well as interactions with the gut microbiota. Perturbances to this system have been found to play a critical role in the development of visceral hypersensitivity, bowel dysregulation, and mood. This review will summarize the principle processes involved in the neurologic and biologic function of the brain-gut axis, our current understanding of its role in functional GI disorders, and potential targets for therapeutic intervention.