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Gut bacterial and fungal signatures in relation to human leukocyte antigen-DQ2/DQ8 in children with celiac disease and siblings
Dominika Salamon, Agnieszka Krawczyk, Barbara Zapała, Mariusz Duplaga, Kinga Kowalska-Duplaga, Tomasz Gosiewski
Dominika Salamon, Agnieszka Krawczyk, Tomasz Gosiewski, Department of Microbiology, Division of Molecular Medical Microbiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow 31-121, Poland
Barbara Zapała, Centre for Innovative Medical Education, Jagiellonian University Medical College, Krakow 31-066, Poland
Barbara Zapała, Multidisciplinary Clinical Research Support Center, 5th Military Clinical Hospital with Polyclinic, Krakow 30-090, Poland
Mariusz Duplaga, Department of Health Promotion and e-Health, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow 31-066, Poland
Kinga Kowalska-Duplaga, Department of Pediatrics, Gastroenterology and Nutrition, Faculty of Medicine, Jagiellonian University Medical College, Krakow 30-663, Poland
Co-corresponding authors: Kinga Kowalska-Duplaga and Tomasz Gosiewski.
Author contributions: Gosiewski T, Salamon D, and Kowalska-Duplaga K contributed to conceptualization and writing of review and editing; Gosiewski T, Salamon D, and Krawczyk A contributed to methodology; Zapala B and Duplaga M contributed to formal analysis; Salamon D, Gosiewski T, Kowalska-Duplaga K, and Krawczyk A contributed to investigation; Duplaga M and Zapala B contributed to data curation; Salamon D wrote original draft; Gosiewski T performed project administration; Kowalska-Duplaga K and Gosiewski T did supervision and made equal contributions as co-corresponding authors. All authors approved the final version of the article.
Supported by National Science Centre in Poland, No. 2017/26/E/NZ5/00266.
Institutional review board statement: All procedures involving human participants were approved by the Jagiellonian University Bioethics Committee in Krakow, Poland, No. 1072.6120.82.2018.
Informed consent statement: Informed consent was obtained from patients’ parents or legal guardians (for all patients under 18 years of age) and, additionally, from patients themselves if they were above 16 years old.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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.
Corresponding author: Tomasz Gosiewski, PhD, Full Professor, Department of Microbiology, Division of Molecular Medical Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 18 Czysta Street, Krakow 31-121, Poland.
tomasz.gosiewski@uj.edu.pl
Received: November 6, 2025
Revised: December 6, 2025
Accepted: January 14, 2026
Published online: March 14, 2026
Processing time: 117 Days and 13.8 Hours
BACKGROUND
The presence of human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 alleles is necessary but not sufficient for the development of celiac disease (CeD). This suggests that additional environmental and biological factors, including bacteria and, above all, the still rarely studied fungal gut microbiota, play key roles in disease onset and progression.
AIM
To characterize and compare the intestinal bacteriobiota and mycobiota profiles of children with newly diagnosed CeD and their unaffected siblings, in comparison with a healthy control group.
METHODS
The study included children and adolescents aged 1 to 18 years. Participants were divided into three groups: (1) 14 patients with newly diagnosed CeD; (2) 16 asymptomatic siblings of CeD patients; and (3) 19 healthy children (control group). Stool samples were collected from all eligible participants. Next-generation sequencing was performed, followed by analysis of the relationship between the gut microbiota and genetic predisposition to CeD, with attention to the HLA DQ2/8 alleles.
RESULTS
Regarding alpha diversity, the CeD and sibling groups differed significantly from the control group (bacteria), and the CeD group differed from siblings (fungi). Significant dissimilarities in beta diversity were observed between siblings and both CeD and control groups. In comparisons between CeD group and their siblings, 13 indicator bacterial species were identified, whereas in comparisons between the CeD group and their siblings and controls, 8 indicator fungal species were detected. No significant correlation was found between bacterial species and the presence of the HLA DQ2.5 allele, or between fungal species and HLA DQ2.2. A strong (r = 0.8-0.9) positive relationship was found between Subdoligranulum variabile and several bacterial species. A moderate (r = 0.4-0.7) positive correlation was observed between the fungal species Microidium phyllanthi and Bifidobacterium longum, Clostridium leptum and Romboutsia timonensis.
CONCLUSION
While DQ2.5 plays a central role in disease pathogenesis, it appears to have less direct influence on microbial composition. The distinct fungal signatures observed in siblings may serve as early indicators of risk and warrant further investigation.
Core Tip: This is the first comprehensive assessment of the bacteriobiome and mycobiome in children with celiac disease (CeD) and their first-degree relatives (siblings). Our findings highlight the potential of both bacterial and fungal signatures as early biomarkers of CeD susceptibility and suggest that host human leukocyte antigen genotypes, particularly DQ8 and DQ2.2, may shape the gut microbial landscape in children at risk for CeD, through both bacterial and fungal communities.
