Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2023; 29(14): 2172-2187
Published online Apr 14, 2023. doi: 10.3748/wjg.v29.i14.2172
Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease
Agnieszka Krawczyk, Dominika Salamon, Kinga Kowalska-Duplaga, Barbara Zapała, Teofila Książek, Marta Drażniuk-Warchoł, Tomasz Gosiewski
Agnieszka Krawczyk, Dominika Salamon, Tomasz Gosiewski, Department of Microbiology, Division of Molecular Medical Microbiology, Jagiellonian University Medical College, Cracow 31-121, Poland
Kinga Kowalska-Duplaga, Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College, Cracow 30-663, Poland
Barbara Zapała, Department of Clinical Biochemistry, Jagiellonian University Medical College, Cracow 31-066, Poland
Teofila Książek, Department of Medical Genetics, Jagiellonian University Medical College, Cracow 30-663, Poland
Marta Drażniuk-Warchoł, Department of Pediatrics, Gastroenterology and Nutrition, University Children's Hospital, Cracow 30-663, Poland
Author contributions: Krawczyk A performed the molecular investigations, interpreted the data, prepared the tables and figures, and wrote the manuscript; Kowalska-Duplaga K recruited patients, and revised the paper; Zapała B analyzed data, and revised the paper; Książek T performed the investigations; Drażniuk-Warchoł M recruited patients; Salamon D, and Gosiewski T coordinated the study, interpreted data, and revised the article; all authors approved the final version of the article.
Supported by National Science Centre (Poland), No. 2019/33/N/NZ5/00698.
Institutional review board statement: The study was reviewed and approved by the Jagiellonian University Bioethics Committee, No. 1072.6120.21.2020.
Informed consent statement: All participants received explanations about the study objectives and expected results, having been enrolled in the study only after signing the informed consent form.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Fastq files are available from The Jagiellonian University Repository-online access: https://ruj.uj.edu.pl/xmlui/handle/item/304597
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: Tomasz Gosiewski, MSc, PhD, Full Professor, Department of Microbiology, Division of Molecular Medical Microbiology, Jagiellonian University Medical College, Faculty of Medicine, Czysta 18 Str., Cracow 31-121, Poland. tomasz.gosiewski@uj.edu.pl
Received: December 21, 2022
Peer-review started: December 21, 2022
First decision: January 3, 2023
Revised: January 13, 2023
Accepted: March 9, 2023
Article in press: March 9, 2023
Published online: April 14, 2023
Processing time: 112 Days and 22.7 Hours
Abstract
BACKGROUND

Numerous studies have shown that in Crohn’s disease (CD), the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract. Until recently, studies have focused almost exclusively on bacteria in the gut. Lately, more attention has been paid to the role of intestinal fungi.

AIM

To study the gut mycobiome analysis of pediatric patients with CD (in different stages of disease activity) compared to healthy children.

METHODS

Fecal samples were collected from patients: With active, newly diagnosed CD (n = 50); active but previously diagnosed and treated CD (n = 16); non-active CD and who were in clinical remission (n = 39) and from healthy volunteers (n = 40). Fungal DNA was isolated from the samples. Next, next generation sequencing (MiSeq, Illumina) was performed. The composition of mycobiota was correlated with clinical and blood parameters.

RESULTS

Candida spp. were overrepresented in CD patients, while in the control group, the most abundant genus was Saccharomyces. In CD patients, the percentage of Malassezia was almost twice that of the control (P < 0.05). In active CD patients, we documented a higher abundance of Debaryomyces hansenii (D. hansenii) compared to the non-active CD and control (P < 0.05) groups. Moreover, statistically significant changes in the abundance of Mycosphaerella, Rhodotorula, and Microidium were observed. The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population. Moreover, we have documented statistically significant correlations between: D. hansenii and patient age (negative); C. zeylanoides and patient age (positive); C. dubliniensis and calprotectin (positive); C. sake and calprotectin (positive); and C. tropicalis and pediatric CD activity index (PCDAI) (positive).

CONCLUSION

Mycobiome changes in CD patients, and the positive correlation of some species with calprotectin or PCDAI, give strong evidence that fungi may be of key importance in the development of CD.

Keywords: Intestinal mycobiome; Fungi; Crohn’s disease; Inflammatory bowel disease; Next generation sequencing; Molecular microbiology

Core Tip: There is growing evidence that intestinal microorganisms are associated with pathogenesis of Crohn’s disease (CD). Until recently, studies have focused almost exclusively on bacteria. In this study we showed alterations in the fungal composition in pediatric patients with CD. Changes within the specific species of fungi depending on disease activity, and the positive correlation of some species with calprotectin or pediatric CD activity index, give strong evidence that these microorganisms may be of key importance in the development and course of CD. Some fungal species can be helpful in predicting an exacerbation of the disease or even predicting the diagnosis of CD.