Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 3098-3109
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3098
Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations
Ai-Juan Xue, Shi-Jian Miao, Hua Sun, Xiao-Xia Qiu, Sheng-Nan Wang, Lin Wang, Zi-Qing Ye, Cui-Fang Zheng, Zhi-Heng Huang, Yu-Huan Wang, Ying Huang
Ai-Juan Xue, Shi-Jian Miao, Hua Sun, Xiao-Xia Qiu, Sheng-Nan Wang, Lin Wang, Zi-Qing Ye, Cui-Fang Zheng, Zhi-Heng Huang, Yu-Huan Wang, Ying Huang, Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai 201102, China
Author contributions: Xue AJ, Huang Y, Miao SJ, Sun H, Qiu XX, Wang SN, Wang L, Ye ZQ, Zheng CF, Wang YH, and Huang ZH contributed to study conception and design; Xue AJ, Miao SJ, Sun H, Qiu XX, and Wang SN contributed to data acquisition and interpretation; Xue AJ contributed to the first draft of this article; Xue AJ, Miao SJ, Sun H, Qiu XX, Wang SN, Wang L, Ye ZQ, Zheng CF, Huang ZH, Wang YH, and Huang Y contributed to editing, reviewing, and final approval of the article.
Supported by the Jiujiu Charitable Trust-PIBD China.
Institutional review board statement: This study was approved by the Ethics Board of the Children's Hospital of Fudan University (2017-229, Shanghai).
Informed consent statement: Oral or written informed consent was obtained from the parents or guardians of the children prior to sample collection.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The dataset is available from the corresponding author at yhuang2019@126.com.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
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: Ying Huang, MD, PhD, Doctor, Department of Gastroenterology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China. yhuang2019@126.com
Received: January 6, 2020
Peer-review started: January 6, 2020
First decision: January 19, 2020
Revised: March 30, 2020
Accepted: May 28, 2020
Article in press: May 28, 2020
Published online: June 14, 2020

Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome.


To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity.


Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.


Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.


In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

Keywords: IL10RA gene, Gut microbiota, Pediatric, Crohn's disease, Disease severity

Core tip: Understanding the role of microbes in sub-populations of inflammatory bowel disease patients is important. The focus on this relatively unique and uniform interleukin (IL)10RA group provides an excellent opportunity. In this study, clinical variables of IL10RA-deficient patients (such as disease course) were linked with changes in the stool microbiome, which implies potential clinical relevance of the changes in microbial populations.