title: The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease.
abstract: OBJECTIVE
  Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD.
  
  
  METHODS
  As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR.
  
  
  RESULTS
  Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium).
  
  
  CONCLUSIONS
  The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.
authors.affiliation: Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Olivares
authors.affiliation: Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Neef
authors.affiliation: Hospital Universitario Sant Joan de Reus, Tarragona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Castillejo
authors.affiliation: Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: G De
authors.initials: GD
authors.lastname: Palma
authors.affiliation: Gastroenterología, Nutrición y Hepatología Pediátrica, Hospital Universitario Sant Joan de Deu and Unidad de Gastroenterología Pediátrica del Institut Dexeus, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Varea
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF) and IBV-CSIC Associated Unit, CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Capilla
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF) and IBV-CSIC Associated Unit, CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.affiliation: Department Metabolismo y Nutrición, ICTAN-CSIC, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Nova
authors.affiliation: Department Metabolismo y Nutrición, ICTAN-CSIC, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Marcos
authors.affiliation: Servicio de Gastroenterología y Nutrición Pediátrica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Polanco
authors.affiliation: Unidad de Gastroenterología Pediátrica, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ribes-Koninckx
authors.affiliation: Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canarias, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Ortigosa
authors.affiliation: Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Izquierdo
authors.affiliation: Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Sanz
mesh_terms: D002446:Celiac Disease / Q000235:genetics* / Q000382:microbiology; D003013:Clostridium / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007422:Intestines / Q000382:microbiology*; D008297:Male; D064307:Microbiota / Q000235:genetics*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen
keywords: Bifidobacteria; Celiac Disease; Intestinal Bacteria