Clinical Trials Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2021; 27(18): 2219-2237
Published online May 14, 2021. doi: 10.3748/wjg.v27.i18.2219
Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome
Magdy El-Salhy, Christina Casen, Jørgen Valeur, Trygve Hausken, Jan Gunnar Hatlebakk
Magdy El-Salhy, Department of Medicine, Stord Helse-Fonna Hospital, Stord 5416, Norway
Magdy El-Salhy, Trygve Hausken, Jan Gunnar Hatlebakk, Department of Clinical Medicine, University of Bergen, Bergen 5020, Norway
Magdy El-Salhy, Trygve Hausken, Jan Gunnar Hatlebakk, National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5020, Norway
Christina Casen, Genetic Analysis AS, Oslo 0485, Norway
Jørgen Valeur, Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo 0440, Norway
Author contributions: El-Salhy M designed the study, obtained the funding, administered the study, recruited the patients, performed faecal microbiota transplantation, collected, analyzed and interpreted the data, and drafted the manuscript; Casen C contributed to the design of the study, analyzed the faecal bacteria and critically revised the manuscript for important intellectual content; Valeur J contributed to the design of the study, analyzed the short-chain fatty acids and critically revised the manuscript for important intellectual content; Hausken T and Hatlebakk JG contributed to the design of the study and to the analysis and interpretation of the data, and critically revised the manuscript for important intellectual content.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the University of Bergen.
Clinical trial registration statement: This study is registered at (NCT03822299) and (ID657402).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrolment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
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:
Corresponding author: Magdy El-Salhy, BSc, MD, PhD, Chief Doctor, Professor, Department of Medicine, Stord Helse-Fonna Hospital, Tysevegen 64, Stord 5416, Norway.
Received: January 25, 2021
Peer-review started: January 25, 2021
First decision: February 27, 2021
Revised: March 13, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 14, 2021
Research background

Irritable bowel syndrome (IBS) is a common chronic disorder, where intestinal microbiota plays a pivotal role in its pathophysiology. Faecal microbiota transplantation for IBS appears to be a promising treatment of IBS.

Research motivation

In Western countries, there is a female predominance in IBS with female:male ratio of 2:1. In a recent randomized double-blind placebo-controlled trial on faecal microbiota transplantation (FMT) in IBS females responded better to FMT than did males.

Research objectives

We aimed to investigate whether there is a sex difference in the response to FMT in terms of symptoms, dysbiosis, and bacteria and short-chain fatty acids (SCFAs) profiles in the same cohort of patients that we had investigated in our previous randomized controlled trial.

Research methods

This study included 164 patients who fulfilled the Rome IV criteria for the diagnosis of IBS. These patient’s cohort included IBS diarrhoea-predominant (IBS-D), IBS-constipation predominant (IBS-C) and mixed diarrhoea and constipation (IBS-M) subtypes. They were randomized to placebo (own faeces), 30 g or 60 g donor’s faeces at a ratio of 1:1:1. The faecal transplant was administered via gastroscope to the duodenum. Patients completed IBS severity scoring system (IBS-SSS), the Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. Response was defined as a decrease of ≥ 50 points in the IBS-SSS total score after FMT. The faecal bacteria profile and dysbiosis were determined by the GA-map Dysbiosis Test (Genetic Analysis, Oslo, Norway) using the 16S rRNA gene. The levels of faecal SCFAs were determined by gas chromatography.

Research results

There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with IBS-D than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT.

Research conclusions

There is no sex difference in the response to FMT in IBS patients with moderate-to-severe IBS symptoms belonging to the three of IBS subtypes of IBS-C and IBS-M in patients who did not responded to National Institute for Health and Care Excellence-modified diet. However, female patients with IBS-D had a significant higher response rate to FMT and lower IBS-SSS score after FMT than males.

Research perspectives

The present observation that female patients with IBS-D respond better to FMT than males raise several questions as to the cause of this difference. Further studies are needed to explore the difference in diet and life style between females and males as possible causes for this difference.