Published online May 12, 2020. doi: 10.4291/wjgp.v11.i3.64
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
Currently, inflammatory bowel diseases (IBD) diagnostics features several challenges mainly related to its accurate differentiation from other disease with similar symptoms. In the last years, some studies have shown that the abundance of Faecalibacterium prausnitzii (F. prausnitzii) is a potential biomarker to discriminate between gut disorders. This species load in conjunction with Escherichia coli (E. coli) abundance (F-E index) has been proven to be a better biomarker than total F. prausnitzii alone. Besides, the quantification of F. prausnitzii phylogroup I and phylogroup II has been proposed as a source of additional information to discriminate within IBD. However, the usefulness of an index including the quantification of the phylogroups in conjunction with E. coli remains to be explored, and also its applicability to tell apart these conditions from other gut disorders with milder or worsen phenotypes.
Currently, IBD diagnosis involves a comprehensive examination of the patient that includes clinical, endoscopic, radiologic, and histological criteria. In addition, as clinical manifestations of IBD are unstable during the disease course, a long monitoring period is needed to classify the disease phenotype accurately. As IBD patients feature an imbalanced gut microbial community in comparison to healthy subjects, in the last years the implementation of bacteria representative of this dysbiosis as biomarkers has been started to be explored as a novel strategy to support IBD diagnostics and/or prognostics.
The main objective of this study was to evaluate six options of bacterial biomarkers in terms of their capability to discriminate IBD from other gut disorders and within IBD subtypes.
Adult males and females undergoing routine colonoscopy at the Hospital Dr. Josep Trueta and Parc Hospitalari Martí i Julià in Girona (Spain) were asked to participate, providing either biopsy and/or faecal samples. Subjects included healthy controls as well as patients with IBD, CRC or irritable bowel syndrome (IBS). Genomic DNA extracts of samples were used to assess the load of bacterial markers candidates (total F. prausnitzii, phylogroup I and II of this species and E. coli) by qPCR using specific primers previously reported. Relative abundances to total Bacteria present in the sample, and indices combining F. prausnitzii and E. coli were calculated. Biomarkers accuracy to discriminate conditions was measured by the area under the receiver operating characteristic curve (AUC). To the best of our knowledge, this is the first study that tests combination of F. prausnitzii phylogroups and E. coli application to assist in discriminating challenging IBD diagnostic conditions, compares their performance with previously reported biomarkers and further corroborates results in non-invasive samples.
This study reveals that the F-E index would be the choice to discriminate IBD from colorectal cancer (CRC), especially from ulcerative colitis (UC), regardless of the activity status of the patient and irrespectively if a colonic or a rectal sample was used. This observation is of particular relevance because there is an association between IBD (especially those involving colonic inflammation) and the risk of CRC. Besides, we have observed that PHG I-E index is a good parameter to differentiate pancolitis from other UC subtypes, which is of interest for clinicians to monitor risk of progression of the inflamed area. The application of bacterial biomarkers in feces is also demonstrated, which is a non-invasive method and may represent a step forward to implement these biomarkers in clinical practice to support IBD diagnostics.
This study corroborates that F. prausnitzii combined with E. coli can help to discriminate within IBD subtypes both in tissue and fecal samples, as well as offer potential to differentiate IBD and CRC patients. Use of biopsy samples presented better performance, but we confirmed that suitable results in fecal samples were shown too. The comparison of the performance of new indices with those previously reported in the literature has allowed establishing the biomarker of choice to select depending on the conditions to discriminate. From these comparisons, we hypothesize that given the complexity of the disease in terms of multiple subtypes and phenotypes during the disease course, it would be complicated the establishment of a universal biomarker using only two species and total microbiota composition could be a more informative approximation in this regard. However, given the outcome obtained only with the biomarkers evaluated here, we envisage that implementation of bacterial load assessment in clinical routine may ease IBD diagnostics in the future, for example for initial screening.
This study contributes to providing evidence that bacterial biomarkers assessment may help in solving intestinal disorders diagnostic challenges. Because differences in performance were observed between tissue and faecal samples, attention should be paid to this issue in similar studies. Future directions of research could assess if discrimination between gut conditions is enhanced when these bacterial indicators are combined with other bacterial or serologic biomarkers of intestinal disease. Also, validation in a larger cohort of completely independent patients, including volunteers from different regions would be required to define a tool with worldwide application in clinical routine.