Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine

G De Palma1, A Capilla, I Nadal

  • 1Ecofisicologia Microbiana, Instituto de Agroquimica y Tecnologia de Alimentos (CSIC), Valencia, Spain.

Insights

Genetic predisposition to coeliac disease (CD) influences early gut bacteria colonization in infants. Higher-risk infants show distinct microbial profiles, suggesting a link between HLA-DQ genes and gut microbiome development.

Area of Science:

  • Microbiome research
  • Genetics
  • Pediatric gastroenterology

Background:

  • Coeliac disease (CD) development is multifactorial, involving genetic predisposition (HLA-DQ2/DQ8) and environmental triggers.
  • The early gut microbiome plays a crucial role in immune system development and may influence CD pathogenesis.
  • Understanding the interplay between host genetics and the infant gut microbiome is key to deciphering CD etiology.

Purpose of the Study:

  • To investigate the influence of human leukocyte antigen (HLA)-DQ genotype on the gut microbial colonization process in breast-fed infants at risk for CD.
  • To determine if genetic risk stratification correlates with specific bacterial group abundances in early life.

Main Methods:

  • A cohort of 20 newborns with a family history of CD were genotyped for HLA-DQ risk.
  • Faecal microbiota was analyzed at 7 days, 1 month, and 4 months using fluorescence in situ hybridization (FISH).
  • Bacterial group proportions were compared across high, intermediate, and low genetic risk groups.

Main Results:

  • Infants with high genetic risk for CD exhibited significantly higher proportions of Gram-negative bacteria and the Bacteroides-Prevotella group compared to intermediate and low-risk groups.
  • Specific bacterial groups, including E. coli, Streptococcus-Lactococcus, and sulphate-reducing bacteria, were elevated in high-risk infants.
  • These microbial differences correlated with genetic risk and were influenced by the number and type of CD relatives.

Conclusions:

  • The study suggests a significant relationship between HLA-DQ genes and the gut microbial colonization patterns in infants at risk for CD.
  • These findings indicate that genetic predisposition may shape the early gut microbiome, potentially contributing to CD development.
  • This research opens new avenues for investigating CD by considering the host-microbiome-gene interactions from infancy.

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