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Published on: August 10, 2018
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.
Abstract:
Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.
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