Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2018; 24(46): 5223-5233
Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5223
Modulation of faecal metagenome in Crohn’s disease: Role of microRNAs as biomarkers
María Rojas-Feria, Teresa Romero-García, Jose Ángel Fernández Caballero-Rico, Helena Pastor Ramírez, Marta Avilés-Recio, Manuel Castro-Fernandez, Natalia Chueca Porcuna, Manuel Romero-Gόmez, Federico García, Lourdes Grande, José A Del Campo
María Rojas-Feria, Teresa Romero-García, Marta Avilés-Recio, Manuel Castro-Fernandez, Lourdes Grande, José A Del Campo, Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Seville E-41014, Spain
Jose Ángel Fernández Caballero-Rico, Natalia Chueca Porcuna, Federico García, Complejo Hospitalario Universitario de Granada, Microbiology, Granada E-18016, Spain
Jose Ángel Fernández Caballero-Rico, Facultad de ciencias de la salud. Universidad Europea Miguel de Cervantes, Madrid E-28280, Spain
Helena Pastor Ramírez, Manuel Romero-Gόmez, Institute of Biomedicine of Seville, Digestive Diseases, Hospital Universitario Virgen del Rocío and CIBERehd, Seville E-41013, Spain
Author contributions: Rojas-Feria M, Romero-García T, Romero-Gómez M, García F, Grande L and Del Campo JA; designed the study and wrote the manuscript. Fernández Caballero-Rico JÁ, Pastor Ramírez H and Avilés-Recio M; analyzed the data. Rojas-Feria M, Castro-Fernández M, Chueca Porcuna N, Grande L and Del Campo JA; contributed to perform experiments and data analysis
Supported by Instituto de Salud Carlos III, and Consejería de Salud Junta de AndalucíaPI14/01349.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Valme Hospital of Seville University.
Conflict-of-interest statement: All authors declare there are no competing interests in this study.
Data sharing statement: All data regarding this manuscript will be available upon request.
ARRIVE guidelines statement: The manuscript was prepared according to the ARRIVE Guidelines.
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 to: José A Del Campo, PhD, Senior Scientist, Department of Digestive Diseases, Valme University Hospital, UGC Digestive Disease and CIBERehd, Servicio Andaluz de Salud, Avda. Bellavista s/n, Sevilla E-41014, Spain.
Telephone: +34-95-5015485
Received: September 19, 2018
Peer-review started: September 19, 2018
First decision: November 1, 2018
Revised: November 13, 2018
Accepted: November 16, 2018
Article in press: November 16, 2018
Published online: December 14, 2018
Research background

Pathogenesis of inflammatory bowel disease (IBD) has not been clarified yet. The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. The causality between IBD and alterations in microbiota remains incompletely understood but one theory is that altered microbiota composition and function in IBD result in increased immune stimulation or enhanced mucosal permeability. On the other hand, microRNAs (miRNAs) have been involved in the pathogenesis of IBD and have been explored as biomarkers and therapeutic targets. It has been shown that miRNAs regulate specific genes associated with Crohn´s disease (CD).

Research motivation and objectives

Identification of host and microbiota alterations in individual patients should lead to selective target interventions. In this study, we first analyzed the faecal microbiota composition in CD patients at the time of diagnosis. Secondly, we compared miRNA expression in CD gut samples obtained from endoscopically normal and affected mucosa, in order to find a marker of active IBD.

Research methods

In this study, we will use deep-sequencing methods to analyze the microbiota from patients with CD and healthy controls. Moreover, a miRNAs screening will be performed to identify individual miRNA involved in inflammation process that could serve as biomarkers for disease progression on therapeutic target.

Research results

We found significant differences in microbiota composition when comparing patients with CD compared to the control population. The major differences were found in microbial biodivertiy (Shannon Index). We also found a reduction in Firmicutes and an increase in Bacteroidetes. Clostridia class was also significantly reduced in Crohn’s disease group.

Research conclusions

We found that active non-treated CD patients had a low Firmicutes/Bacteroidetes ratio, less biodiversity in the structure of microbial communities and a significantly different pattern on gut microbiota distribution. Moreover, microbiota metabolism was altered in CD patients compared to healthy subjects. This data strongly suggests that dysbiosis may play a role in the pathogenesis of CD. Three miRNAs have been found induced in affected mucosa vs non-affected mucosa in CD, indicating that miRNA profile may serve as a biomarker for active disease.

Research perspectives

Additional studies are needed to validate the results obtained and to identify causative roles for the microbiota. The role of miRNAs in the pathogenesis or diagnosis of IBD, including CD must be established through deeper analysis and validation in circulating tissues.