PMID- 24939571 OWN - NLM STAT- MEDLINE DCOM- 20150420 LR - 20150204 IS - 1468-3288 (Electronic) IS - 0017-5749 (Linking) VI - 64 IP - 3 DP - 2015 Mar TI - The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. PG - 406-17 LID - 10.1136/gutjnl-2014-306931 [doi] AB - 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. DESIGN: 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. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Olivares, M AU - Olivares M AD - Instituto de Agroquimica y Tecnologia de Alimentos, Consejo Superior de Investigaciones Cientificas (IATA-CSIC), Valencia, Spain. FAU - Neef, A AU - Neef A AD - Instituto de Agroquimica y Tecnologia de Alimentos, Consejo Superior de Investigaciones Cientificas (IATA-CSIC), Valencia, Spain. FAU - Castillejo, G AU - Castillejo G AD - Hospital Universitario Sant Joan de Reus, Tarragona, Spain. FAU - Palma, G De AU - Palma GD AD - Instituto de Agroquimica y Tecnologia de Alimentos, Consejo Superior de Investigaciones Cientificas (IATA-CSIC), Valencia, Spain. FAU - Varea, V AU - Varea V AD - Gastroenterologia, Nutricion y Hepatologia Pediatrica, Hospital Universitario Sant Joan de Deu and Unidad de Gastroenterologia Pediatrica del Institut Dexeus, Barcelona, Spain. FAU - Capilla, A AU - Capilla A AD - Centro de Investigacion Principe Felipe (CIPF) and IBV-CSIC Associated Unit, CIBER de Enfermedades Raras (CIBERER), Valencia, Spain. FAU - Palau, F AU - Palau F AD - Centro de Investigacion Principe Felipe (CIPF) and IBV-CSIC Associated Unit, CIBER de Enfermedades Raras (CIBERER), Valencia, Spain. FAU - Nova, E AU - Nova E AD - Department Metabolismo y Nutricion, ICTAN-CSIC, Madrid, Spain. FAU - Marcos, A AU - Marcos A AD - Department Metabolismo y Nutricion, ICTAN-CSIC, Madrid, Spain. FAU - Polanco, I AU - Polanco I AD - Servicio de Gastroenterologia y Nutricion Pediatrica, Hospital Universitario La Paz, Madrid, Spain. FAU - Ribes-Koninckx, C AU - Ribes-Koninckx C AD - Unidad de Gastroenterologia Pediatrica, Hospital Universitario La Fe, Valencia, Spain. FAU - Ortigosa, L AU - Ortigosa L AD - Unidad de Gastroenterologia, Hepatologia y Nutricion Pediatrica, Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Canarias, Spain. FAU - Izquierdo, L AU - Izquierdo L AD - Instituto de Agroquimica y Tecnologia de Alimentos, Consejo Superior de Investigaciones Cientificas (IATA-CSIC), Valencia, Spain. FAU - Sanz, Y AU - Sanz Y AD - Instituto de Agroquimica y Tecnologia de Alimentos, Consejo Superior de Investigaciones Cientificas (IATA-CSIC), Valencia, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140617 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Genetic Markers) RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DQ2 antigen) SB - IM MH - Celiac Disease/*genetics/microbiology MH - Clostridium/genetics MH - Feces/microbiology MH - Female MH - Genetic Markers/genetics MH - Genotype MH - HLA-DQ Antigens/*genetics MH - Haplotypes/genetics MH - Humans MH - Infant MH - Intestines/*microbiology MH - Male MH - Microbiota/*genetics MH - Prospective Studies MH - Real-Time Polymerase Chain Reaction MH - Risk Factors OTO - NOTNLM OT - Bifidobacteria OT - Celiac Disease OT - Intestinal Bacteria EDAT- 2014/06/19 06:00 MHDA- 2015/04/22 06:00 CRDT- 2014/06/19 06:00 PHST- 2014/06/19 06:00 [entrez] PHST- 2014/06/19 06:00 [pubmed] PHST- 2015/04/22 06:00 [medline] AID - gutjnl-2014-306931 [pii] AID - 10.1136/gutjnl-2014-306931 [doi] PST - ppublish SO - Gut. 2015 Mar;64(3):406-17. doi: 10.1136/gutjnl-2014-306931. Epub 2014 Jun 17.