Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2021; 27(9): 866-885
Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.866
Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease
Katia Farias e Silva, Hayandra F Nanini, Cynthia Machado Cascabulho, Siane L B Rosas, Patricia T Santana, Antonio José de V Carneiro, Elias Anaissie, Marcio Nucci, Heitor Siffert Pereira de Souza
Katia Farias e Silva, Hayandra F Nanini, Siane L B Rosas, Patricia T Santana, Antonio José de V Carneiro, Marcio Nucci, Heitor Siffert Pereira de Souza, Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
Cynthia Machado Cascabulho, Laboratory of Innovations in Therapies, Education and Bioproducts, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil
Elias Anaissie, Clinical Trial and Consulting Services, Cincinnati, OH 45267, United States
Heitor Siffert Pereira de Souza, Internal Medicine, D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil
Author contributions: Farias e Silva K and Carneiro AJV participated in the conception and design of the study, the acquisition, analysis, and interpretation of data, and the drafting of the manuscript; Nanini HF, Cascabulho CM, Rosas SLB, and Santana PT participated in the acquisition, analysis, and interpretation of data; Anaissie E conceptually proposed the idea of gut inflammation and high 1,3-Beta-D-glucan levels and critically revised the manuscript; Nucci M and de Souza HSP participated in the conception and design of the study, obtained funding, analyzed and interpreted the data, and critically revised the manuscript for important intellectual content; all the authors gave final approval of the submitted version of the manuscript.
Supported by The Brazilian Research Council (CNPq), No. 306634/2019-8; The FAPERJ (Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro), No. E26/202.781/2017; and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES), No. 31001017048P0.
Institutional review board statement: The study was reviewed and approved by the Ethical Committee of the Hospital Copa D’Or with the co-participation of the University Hospital of the Federal University of Rio de Janeiro (CAAE: 53351116.1.0000.5249).
Informed consent statement: All study participants provided informed written consent prior to study enrolment.
Conflict-of-interest statement: The authors declare that they have no competing interests to report related to the work submitted for consideration of publication.
Data sharing statement: Technical appendix, statistical code, and dataset supporting the conclusions of this study will be made available from the corresponding author at [hsouza@hucff.ufrj.br], without undue reservation, to any qualified researcher.
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: Heitor Siffert Pereira de Souza, MD, PhD, Associate Research Scientist, Full Professor, Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Cidade Universitaria, Rio de Janeiro 21941-913, Brazil. hsouza@hucff.ufrj.br
Received: November 11, 2020
Peer-review started: November 11, 2020
First decision: December 31, 2020
Revised: January 11, 2021
Accepted: February 18, 2021
Article in press: February 18, 2021
Published online: March 7, 2021
Processing time: 111 Days and 13.6 Hours
ARTICLE HIGHLIGHTS
Research background

Currently, the approach for monitoring the most precise predictors of disease outcomes in inflammatory bowel diseases (IBD), mucosal or histologic remission, demands frequent endoscopic evaluations, which are costly and invasive procedures.

Research motivation

Finding novel non-invasive biomarkers to detect intestinal inflammation continues to represent a major challenge in the field of IBD research.

Research objectives

To determine whether the serum concentrations of beta-glucan (BG), a ubiquitous cell wall component of gut microorganisms, correlate with intestinal inflammation.

Research methods

A prospective observational study was performed in a tertiary referral center, from 2016 to 2019, in which serum BG was determined in patients with Crohn’s disease (CD), ulcerative colitis (UC), and controls, using a photometric detection kit. The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve. Inflammatory activity was determined by ileocolonoscopy, histopathology, magnetic resonance enterography), and biomarkers, including fecal calprotectin, C-reactive protein, and a panel of cytokines. In subgroup analysis, serial BG was used to assess the response to therapeutic interventions.

Research results

The serum BG levels were higher in CD patients than in controls. The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients. Performance analysis showed that the BG results were remarkably better for predicting histologic inflammation than fecal calprotectin and C-reactive protein. Regarding the clinical, endoscopic, and histologic activities, the BG levels were reduced following therapeutic intervention in patients with CD and UC. Compared with and histologic healing, no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography, in CD patients. Positive correlations were detected between BG and interleukin-17 in the CD and the UC group, and between BG and interferon-gamma in the CD group.

Research conclusions

Serum BG concentrations are consistently associated with disease activity in IBD, particularly with histologic inflammation, the ultimate target of treatment.

Research perspectives

Serum BG emerges as an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring IBD.