Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. May 12, 2020; 11(3): 64-77
Published online May 12, 2020. doi: 10.4291/wjgp.v11.i3.64
Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification
Mireia Lopez-Siles, Xavier Aldeguer, Miriam Sabat-Mir, Mariona Serra-Pagès, Sylvia H Duncan, Harry J Flint, L Jesús Garcia-Gil, Margarita Martinez-Medina
Mireia Lopez-Siles, L Jesús Garcia-Gil, Margarita Martinez-Medina, Laboratory of Molecular Microbiology, Biology Department, Universitat de Girona, Girona 17003, Spain
Xavier Aldeguer, Department of Gastroenterology, Hospital Universitari Dr. Josep Trueta, Girona 17007, Spain
Miriam Sabat-Mir, Department of Gastroenterology, Hospital Santa Caterina, Salt 17190, Spain
Mariona Serra-Pagès, GoodGut SL, Girona 17003, Spain
Sylvia H Duncan, Harry J Flint, Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom
Author contributions: Martinez-Medina M and Garcia-Gil LJ contributed to conception and design of the study; López-Siles M, Aldeguer X, Sabat-Mir M and Serra-Pagès M were actively involved in data acquisition; López-Siles M and Martinez-Medina M were involved in data analysis and interpretation; López-Siles M, Martinez-Medina M, Duncan S and Flint H drafted the article; all authors revised the article for important intellectual content and approved the final version of the manuscript.
Supported by the Spanish Ministry of Education and Science, No. SAF2010-15896, No. SAF2013-43284-P and No. SAF2017-82261-P.
Institutional review board statement: This work was reviewed and approved by the Ethics Committee of Clinical Research of the Hospital Universitari Dr. Josep Trueta (Girona, Spain) and the Institut d’Assistència Sanitària of Girona (Salt, Spain) on 24th February 2009 and 21st April 2009, respectively.
Informed consent statement: Informed consent from the subjects was obtained before enrolment.
Conflict-of-interest statement: Aldeguer X is a consultant from AbbVie and has received honoraria for lectures, including services on speakers’ bureaus, from AbbVie, MSD, Shire and Takeda. Aldeguer X, Serra-Pagès, M and Garcia-Gil J own shares in GoodGut S.L. López-Siles M, Garcia-Gil J, Aldeguer X and Martinez-Medina M own patent WO2017025617A1 concerning a Method for the detection, follow up and/or classification of intestinal diseases. The other authors have nothing to disclose.
Data sharing statement: Datasets available from the corresponding author at marga.martinez@udg.edu. Consent was not obtained from participants for data sharing, but the presented data are anonymized, and the risk of identification is low. No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE-Statement-checklist of items.
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: Margarita Martinez-Medina, PhD, Associate Professor, Laboratory of Molecular Microbiology, Biology Department, Universitat de Girona, Carrer de Maria Aurèlia Capmany, 40, Girona 17003, Spain. marga.martinez@udg.edu
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: January 13, 2020
Revised: February 27, 2020
Accepted: March 30, 2020
Article in press: March 30, 2020
Published online: May 12, 2020
Processing time: 133 Days and 12.3 Hours
Abstract
BACKGROUND

The challenges for inflammatory bowel disease (IBD) diagnostics are to discriminate it from gut conditions with similar symptoms such as irritable bowel syndrome (IBS), to distinguish IBD subtypes, to predict disease progression, and to establish the risk to develop colorectal cancer (CRC). Alterations in gut microbiota have been proposed as a source of information to assist in IBD diagnostics. Faecalibacterium prausnitzii (F. prausnitzii), its phylogroups, and Escherichia coli (E. coli) have been reported as potential biomarkers, but their performance in challenging IBD diagnostic situations remains elusive. We hypothesize that bacterial biomarkers based in these species may help to discriminate these conditions of complex diagnostics.

AIM

To evaluate the usefulness of indices calculated from the quantification of these species as biomarkers to aid in IBD diagnostics.

METHODS

A retrospective study of 131 subjects (31 controls (H); 45 Crohn’s disease (CD), 25 ulcerative colitis (UC), 10 IBS, and 20 CRC patients) was performed to assess the usefulness of bacterial biomarkers in biopsies. Further, the performance of biomarkers in faeces was studied in 29 stool samples (19 CD, 10 UC). Relative abundances of total F. prausnitzii (FP), its phylogroups (PHGI and PHGII), and E. coli (E) quantification were determined by qPCR. Loads were combined to calculate the FP-E index, the PHGI–E index and the PHGII-E index. Biomarkers accuracy to discriminate among conditions was measured by the area under the receiver operating characteristic curve (AUC).

RESULTS

In biopsies, FP-E index was good for discriminating IBS from CD (AUC = 0.752) while PHGII-E index was suitable for discriminating IBS from UC (AUC = 0.632). The FP-E index would be the choice to discriminate IBD from CRC, especially from all UC subtypes (AUC ≥ 0.875), regardless of the activity status of the patient. Discrimination between UC patients that had the longest disease duration and those with CRC featured slightly lower AUC values. Concerning differentiation in IBD with shared location, PHGI-E index can establish progression from proctitis and left-sided colitis to ulcerative pancolitis (AUC ≥ 0.800). PHG I-E index analysis in tissue would be the choice to discriminate within IBD subtypes of shared location (AUC ≥ 0.712), while in non-invasive faecal samples FP or PHGI could be good indicators (AUC ≥ 0.833).

CONCLUSION

F. prausnitzii phylogroups combined with E. coli offer potential to discriminate between IBD and CRC patients and can assist in IBD subtypes classification, which may help in solving IBD diagnostics challenges.

Keywords: Crohn’s disease; Ulcerative colitis; Inflammatory bowel disease; Diagnostic tests; Faecalibacterium prausnitzii; Escherichia coli; Irritable bowel syndrome; Colorectal cancer

Core tip: This manuscript evaluates the usefulness of new indexes calculated from the quantification of Faecalibacterium prausnitzii, its phylogroups, and Escherichia coli as biomarkers to assist in challenges of inflammatory bowel disease diagnostics. Firstly, discrimination between inflammatory bowel disease and other intestinal disorders was tested. We present indices to distinguish colorectal cancer from inflammatory bowel disease, especially from subjects with ulcerative colitis. This is of significance given the association between chronic inflammation and the risk of colorectal cancer. In contrast, the proposed indices featured limited performance for discriminating inflammatory bowel disease from irritable bowel syndrome. Secondly, we approach if these biomarkers would be useful to discriminate within inflammatory bowel disease subtypes. We show here good biomarkers to differentiate inflammatory bowel disease subtypes of shared disease location, which may assist in monitoring the risk of progression of the inflamed area. Their application in non-invasive faecal samples is also demonstrated.