Gut Microbiome

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

TL;DR

While HLA-DQ2.5 plays a central role in celiac disease pathogenesis, it appears to have less direct influence on microbial composition, and distinct fungal signatures observed in siblings may serve as early indicators of risk.

Key Findings

Alpha diversity of gut bacteria differed significantly between CeD and sibling groups compared to healthy controls, while fungal alpha diversity differed between CeD and sibling groups.

  • Study included 14 newly diagnosed CeD patients, 16 asymptomatic siblings, and 19 healthy controls aged 1-18 years
  • Bacterial alpha diversity: CeD and sibling groups both differed significantly from the control group
  • Fungal alpha diversity: the CeD group differed significantly from the sibling group
  • Next-generation sequencing of stool samples was used to assess microbiota profiles

Significant dissimilarities in beta diversity (community composition) were observed between the sibling group and both the CeD and control groups.

  • Beta diversity analysis showed the sibling group was compositionally distinct from both CeD patients and healthy controls
  • This suggests asymptomatic siblings have a unique gut microbial community structure not shared with either affected patients or unrelated healthy children
  • Analysis was performed on both bacterial and fungal microbiota from stool samples

Thirteen indicator bacterial species were identified in comparisons between the CeD group and their siblings.

  • Indicator species analysis was used to identify taxa distinguishing between groups
  • 13 bacterial indicator species were detected when comparing CeD patients to their siblings
  • 8 indicator fungal species were detected in comparisons between the CeD group and their combined siblings and controls

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.

  • The analysis specifically examined relationships between HLA alleles DQ2.5 and DQ2.2 and microbial composition
  • Despite HLA-DQ2.5 being the primary genetic risk factor for CeD, it did not significantly correlate with specific bacterial species
  • HLA-DQ2.2 similarly showed no significant correlation with fungal species composition
  • Authors concluded that 'DQ2.5 plays a central role in disease pathogenesis, it appears to have less direct influence on microbial composition'

A strong positive relationship (r = 0.8–0.9) was found between Subdoligranulum variabile and several other bacterial species.

  • Subdoligranulum variabile showed strong positive correlations (r = 0.8–0.9) with multiple bacterial species
  • This suggests co-occurrence or co-regulation patterns within the gut bacterial community in this population
  • Correlation analyses were performed across the study cohort of CeD patients, siblings, and controls

A moderate positive correlation (r = 0.4–0.7) was observed between the fungal species Microidium phyllanthi and the bacterial species Bifidobacterium longum, Clostridium leptum, and Romboutsia timonensis.

  • Microidium phyllanthi is a fungal species whose relationship with gut bacteria is rarely studied
  • Correlations with bacterial species ranged from r = 0.4 to r = 0.7, classified as moderate
  • The three bacterial species correlated with this fungus — Bifidobacterium longum, Clostridium leptum, and Romboutsia timonensis — have various known roles in gut health
  • This cross-kingdom (bacteria-fungi) correlation analysis highlights potential interactions within the gut microbiome in the context of CeD

The fungal gut microbiota (mycobiota) is still rarely studied in the context of celiac disease, and distinct fungal signatures in siblings may serve as early risk indicators.

  • Authors noted that fungal gut microbiota remain understudied compared to bacterial microbiota in CeD
  • The sibling group showed distinct fungal community signatures that differed from both CeD patients and healthy controls
  • Authors proposed that these fungal signatures 'may serve as early indicators of risk and warrant further investigation'
  • Siblings were asymptomatic but genetically at risk due to familial relationship with CeD patients

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Citation

Salamon D, Krawczyk A, Zapała B, Duplaga M, Kowalska-Duplaga K, Gosiewski T. (2026). Gut bacterial and fungal signatures in relation to human leukocyte antigen-DQ2/DQ8 in children with celiac disease and siblings.. World journal of gastroenterology. https://doi.org/10.3748/wjg.v32.i10.116128