Gut bacterial and fungal signatures in relation to human leukocyte antigen-DQ2/DQ8 in children with celiac disease and siblings

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.