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World J Gastroenterol. Feb 7, 2019; 25(5): 539-551
Published online Feb 7, 2019. doi: 10.3748/wjg.v25.i5.539
Contribution of ghrelin to functional gastrointestinal disorders’ pathogenesis
Tilemachos Koutouratsas, Theodora Kalli, Georgios Karamanolis, Maria Gazouli
Tilemachos Koutouratsas, Maria Gazouli, Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens 11527, Greece
Theodora Kalli, Gastroenterology Department, Larnaca General Hospital, Larnaca 6301, Cyprus
Georgios Karamanolis, Gastroenterology Unit, 2nd Department of Surgery, “Aretaieio” University Hospital, School of Medicine, University of Athens, Athens 11527, Greece
Author contributions: All authors equally contributed to this review with conception and design of literature review and analysis, drafting and critical revision and editing, and approval of the final version.
Conflict-of-interest statement: 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:
Corresponding author: Maria Gazouli, PhD, Associate Professor, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, Athens 11527, Greece.
Telephone: +30-210-7462231
Received: November 21, 2018
Peer-review started: November 22, 2018
First decision: December 12, 2018
Revised: December 20, 2018
Accepted: January 14, 2019
Article in press: January 14, 2019
Published online: February 7, 2019
Processing time: 70 Days and 20.6 Hours

Functional gastrointestinal disorders (FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis, exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin’s gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin’s relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.

Keywords: Functional gastrointestinal disorders, Functional colonic diseases, Irritable bowel syndrome, Cyclic vomiting syndrome, Infantile colic, Gastrointestinal disease, Ghrelin, Genetics, Epigenetic processes

Core tip: Functional gastrointestinal disorders are diverse clinical entities whose pathogenesis and phenotype are thought to stem from both genetic and environmental factors. Many reviews have attempted to summarize general pathogenetic mechanisms related to functional gastrointestinal disorders (FGIDs), but more specific knowledge is currently limited. Studies on the brain-gut axis peptide ghrelin have chiefly concentrated on its association with obesity and eating disorders. This review focuses on the possible role of ghrelin in FGID pathogenesis, in an attempt to elucidate the contribution of certain genetic alterations to the emergence of disease.