M Olivares1, A Neef1, G Castillejo2, G De Palma1, V Varea3, A Capilla4, F Palau4, E Nova5, A Marcos5, I Polanco6, C Ribes-Koninckx7, L Ortigosa8, L Izquierdo1, Y Sanz1. 1. Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain. 2. Hospital Universitario Sant Joan de Reus, Tarragona, Spain. 3. Gastroenterología, Nutrición y Hepatología Pediátrica, Hospital Universitario Sant Joan de Deu and Unidad de Gastroenterología Pediátrica del Institut Dexeus, Barcelona, Spain. 4. Centro de Investigación Príncipe Felipe (CIPF) and IBV-CSIC Associated Unit, CIBER de Enfermedades Raras (CIBERER), Valencia, Spain. 5. Department Metabolismo y Nutrición, ICTAN-CSIC, Madrid, Spain. 6. Servicio de Gastroenterología y Nutrición Pediátrica, Hospital Universitario La Paz, Madrid, Spain. 7. Unidad de Gastroenterología Pediátrica, Hospital Universitario La Fe, Valencia, Spain. 8. Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canarias, Spain.
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. 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. 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.
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. 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.
Authors: Jun Wang; Louise B Thingholm; Jurgita Skiecevičienė; Philipp Rausch; Martin Kummen; Johannes R Hov; Frauke Degenhardt; Femke-Anouska Heinsen; Malte C Rühlemann; Silke Szymczak; Kristian Holm; Tönu Esko; Jun Sun; Mihaela Pricop-Jeckstadt; Samer Al-Dury; Pavol Bohov; Jörn Bethune; Felix Sommer; David Ellinghaus; Rolf K Berge; Matthias Hübenthal; Manja Koch; Karin Schwarz; Gerald Rimbach; Patricia Hübbe; Wei-Hung Pan; Raheleh Sheibani-Tezerji; Robert Häsler; Philipp Rosenstiel; Mauro D'Amato; Katja Cloppenborg-Schmidt; Sven Künzel; Matthias Laudes; Hanns-Ulrich Marschall; Wolfgang Lieb; Ute Nöthlings; Tom H Karlsen; John F Baines; Andre Franke Journal: Nat Genet Date: 2016-10-10 Impact factor: 38.330