Case Control Study
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World J Gastroenterol. Aug 14, 2022; 28(30): 4089-4101
Published online Aug 14, 2022. doi: 10.3748/wjg.v28.i30.4089
Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures
Mahasish Shome, Lusheng Song, Stacy Williams, Yunro Chung, Vel Murugan, Jin G Park, William Faubion, Shabana F Pasha, Jonathan A Leighton, Joshua LaBaer, Ji Qiu
Mahasish Shome, Lusheng Song, Stacy Williams, Yunro Chung, Vel Murugan, Jin G Park, Joshua LaBaer, Ji Qiu, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
William Faubion, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, United States
Shabana F Pasha, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Scottsdale, AZ 85259, United States
Jonathan A Leighton, Division of Gastroenterology, Mayo Clinic School of Medicine, Scottsdale, AZ 85259, United States
Author contributions: Shome M and Song L designed and ran the experiment; Williams S and Chung Y performed the statistical analysis; Murugan V and Park JG helped in preparation of clones; Faubion W, Pasha SF and Leighton JA provided the serum samples and also provided intellectual guidance; LaBaer J and Qiu J supervised the project and secured funding; Shome M and Qiu J wrote the original manuscript which was then reviewed by remaining authors.
Institutional review board statement: The authors have taken appropriate steps to protect the rights and welfare of humans participating as subjects in the research (IRB Application #: 13-008267).
Informed consent statement: All study participants or their legal guardian of the study provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data from this study is available on request from the corresponding author.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ji Qiu, PhD, Research Assistant Professor, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 1001 S McAllister Avenue, Tempe, AZ 85281, United States. ji.qiu@asu.edu
Received: April 4, 2022
Peer-review started: April 4, 2022
First decision: May 29, 2022
Revised: June 16, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 14, 2022
ARTICLE HIGHLIGHTS
Research background

Early and accurate diagnosis of inflammatory bowel disease (IBD) can benefit the clinical management of IBD patients. The clinical utility of available non-invasive biomarkers is limited.

Research motivation

The gut microbiota plays an important role in the pathogenesis of IBD. Antibody responses to microbial antigens can be exploited to identify better diagnosis markers and improve our understanding of IBD pathology.

Research objectives

This study aimed to compare anti-microbial antibody profiles in Crohn’s disease (CD) and ulcerative colitis (UC) patients and healthy controls.

Research methods

We employed an innovative protein microarray platform and profiled antibodies against 1570 microbial antigens in 100 CD, 100 UC, and 100 healthy controls.

Research results

Antibodies to bacterial proteins were better in distinguishing IBD patients from healthy controls compared with antibodies to viral proteins. We identified a set of novel anti-microbial antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) elevated in CD patients relative to healthy controls. In addition, anti-microbial antibodies against the antigen of Streptococcus pyogenes (SPy_2009) were found to be elevated in healthy controls relative to UC patients. We constructed antibody panels that could distinguish CD vs control, UC vs control, and CD vs UC with an AUC of 0.81, 0.87 and 0.82 respectively. Patients with severe disease had higher prevalence of anti-microbial antibodies. There was minimal correlation among the occurrence of autoantibodies and anti-microbial antibodies in CD patients.

Research conclusions

This study discovered novel anti-microbial antibodies with differential prevalence in CD and UC patients relative to healthy controls. In addition, this study revealed the potentially different roles of gut microbiota in CD and UC pathology.

Research perspectives

Our study demonstrated the power of a microbiomics approach to identify biomarkers that could aid in the early and accurate detection of IBD non-invasively, and shed light into the role of various microbes in IBD etiology.