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

The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn’s disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.


To investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.


Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.


Microbial community was characterized using 16S rRNA gene sequencing in 29 samples (n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates (P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4).


Changes in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.

Keywords: Crohn’s disease, Dysbiosis, microRNAs, Firmicutes, Bacteroidetes

Core tip: In this study, we have found a shift in microbial gut community composition that supports dysbiosis in Crohn’s disease (CD) patients. The greatest interest of our work is that we have only included new-onset adult CD patients. 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. Three microRNAs (miRNAs) have been found induced in affected mucosa vs non-affected mucosa in CD, indicating that miRNA profile may serve as biomarker for active disease.