Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2022; 28(4): 412-431
Published online Jan 28, 2022. doi: 10.3748/wjg.v28.i4.412
Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome
Eline Margrete Randulff Hillestad, Aina van der Meeren, Bharat Halandur Nagaraja, Ben René Bjørsvik, Noman Haleem, Alfonso Benitez-Paez, Yolanda Sanz, Trygve Hausken, Gülen Arslan Lied, Arvid Lundervold, Birgitte Berentsen
Eline Margrete Randulff Hillestad, Trygve Hausken, Birgitte Berentsen, Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
Eline Margrete Randulff Hillestad, Aina van der Meeren, Ben René Bjørsvik, Noman Haleem, Trygve Hausken, Gülen Arslan Lied, Birgitte Berentsen, National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
Bharat Halandur Nagaraja, Ben René Bjørsvik, Noman Haleem, Arvid Lundervold, Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
Alfonso Benitez-Paez, Host-Microbe Interactions in Metabolic Health Laboratory, Principe Felipe Research Center, Valencia 46012, Spain
Yolanda Sanz, Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council, Paterna-Valencia 46980, Spain
Gülen Arslan Lied, Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
Arvid Lundervold, Department of Biomedicine, University of Bergen, Bergen 5021, Norway
Author contributions: Berentsen B contributed to conceptualization; Hillestad EMR, van der Meeren A, Nagaraja BH, Benitez-Paez A, Sanz Y, Hausken T, Lied GA, Lundervold A, Haleem N and Berentsen B contributed to original draft preparation and writing; Berentsen B edited the manuscript; Lied GA, Lundervold A, Hausken T and Berentsen B supervised this study; Bjørsvik RB contributed critical revision of the manuscript for important intellectual content, and designed the figures; All authors have read and agreed to the published version of the manuscript.
Supported by the Spanish Ministry of Science and Innovation (MICINN, Spain), No. AGL2017-88801-P (to Sanz Y); the Miguel Server grant from the Spanish "Carlos III" Health Institute (ISCIII), No. CP19/00132 (to Benitez-Paez A); The Norwegian Research Council (Funding Post-doc Position for Bharath Halandur Nagaraja), No. FRIMEDBIO276010; and Helse Vest’s Research Funding, No. HV912243; and REA H2020-MSCA-IF-2019, No. 895219 (to Haleem N).
Conflict-of-interest statement: No conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Birgitte Berentsen, MSc, PhD, Associate Professor, National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Jonas Lies vei 65, Bergen 5021, Norway. birgitte.berentsen1@helse-bergen.no
Received: April 17, 2021
Peer-review started: April 17, 2021
First decision: June 3, 2021
Revised: June 24, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: January 28, 2022
Abstract

Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS’ etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.

Keywords: Microbiota, Neurogastroenterology, Irritable bowel syndrome, Microbiota-gut-brain axis, Structural and functional magnetic resonance imaging, Machine learning, Big data analysis

Core Tip: Molecular biology, advanced neuroimaging and computer science is emerging to transform our understanding of the role of gut microbiota in irritable bowel syndrome (IBS). Herein, we provide an overview and discuss the role of gut microbiota in IBS, the clinical microbiota-altering interventions the low FODMAP diet and fecal microbiota transplantation, the role of brain-imaging and gut microbiota analyses, the importance of method selection, metadata, perspectives for improving microbiota role predictions, and big data analysis, in the seeking of understanding IBS pathology.