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World J Gastroenterol. Mar 14, 2019; 25(10): 1185-1196
Published online Mar 14, 2019. doi: 10.3748/wjg.v25.i10.1185
Personalized medicine in functional gastrointestinal disorders: Understanding pathogenesis to increase diagnostic and treatment efficacy
Xiao Jing Wang, Michael Camilleri
Xiao Jing Wang, Michael Camilleri, Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: The authors contributed equally to writing and revising the manuscript. Wang XJ and Camilleri M drafted and finalized the manuscript.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Michael Camilleri, MD, Doctor, Professor, Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, United States. camilleri.michael@mayo.edu
Telephone: +1-507-2662305
Received: January 17, 2019
Peer-review started: January 18, 2019
First decision: January 30, 2019
Revised: February 4, 2019
Accepted: February 22, 2019
Article in press: February 23, 2019
Published online: March 14, 2019
Processing time: 56 Days and 9.7 Hours
Abstract

There is overwhelming evidence that functional gastrointestinal disorders (FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms (UGI Sx). Among patients with UGI Sx, approximately equal proportions (25%) of patients have delayed gastric emptying (GE), reduced gastric accommodation (GA), both impaired GE and GA, or neither, presumably due to increased gastric or duodenal sensitivity. Treatments targeted to the underlying pathophysiology utilize prokinetics, gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia (with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome (IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2D6, 2C19 and 3A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here; pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.

Keywords: Gastrointestinal symptoms; Gastric emptying; Gastric accommodation; Diarrhea; Constipation; Irritable bowel syndrome; Bile acid diarrhea; Phenotypes; Pharmacogenomics; Prokinetics; Neuromodulators

Core tip: Functional gastrointestinal disorders (FGIDs) are associated with mechanisms that constitute important targets for personalized treatment. Patients with upper gastrointestinal (GI) symptoms may have delayed gastric emptying (GE), reduced gastric accommodation (GA), both impaired GE and GA, or neither. Treatments targeted to the underlying pathophysiology utilize prokinetics, gastric relaxants, or central neuromodulators. Patients with functional lower GI symptoms may have constipation-predominant irritable bowel syndrome, pelvic floor dyssynergia, colonic inertia, diarrhea-predominant irritable bowel syndrome, bile acid diarrhea, or disaccharidase or sucrose-isomaltase deficiency. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2D6, 2C19 and 3A4. The time for personalized treatments of FGIDs is here.