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Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease.

Leonard MM, Camhi S, Huedo-Medina TB, Fasano A - Nutrients (2015)

Bottom Line: Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli.These include birthing delivery mode, infant feeding, and antibiotic use.Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

View Article: PubMed Central - PubMed

Affiliation: Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA. mleonard7@mgh.harvard.edu.

ABSTRACT
In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

No MeSH data available.


Related in: MedlinePlus

Study scheme outlining the recruitment and projected incidence of celiac disease (CD) and related HLA genotypes for participants in the Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic Study.
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nutrients-07-05470-f002: Study scheme outlining the recruitment and projected incidence of celiac disease (CD) and related HLA genotypes for participants in the Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic Study.

Mentions: Our power assumptions (Figure 2) are based on our recently published data [5,6]. Assuming that: (a) 500 infants will be enrolled during the pilot period and that the drop rate will be no more than 20% given the duration of the study and similar to that we had with our previous studies, [5,6] 400 infants will complete the pilot protocol; (b) the expected probability of CD serum auto antibodies positivity at 18–24 months in first-degree relatives is 10% irrespective of the HLA compatibility; (c) 70% of first degree relatives are HLA DQ2 and/or DQ8 positive (based on our preliminary data); (d) based on points a and b, the expected probability of CD serum auto antibody positivity at 18–24 months in HLA-compatible first degree relatives is 13.3%; (e) the minimal detectable change in CD autoimmunity probability is 10%, we anticipate that during the study period approximately 50 infants will develop CD.


Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease.

Leonard MM, Camhi S, Huedo-Medina TB, Fasano A - Nutrients (2015)

Study scheme outlining the recruitment and projected incidence of celiac disease (CD) and related HLA genotypes for participants in the Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic Study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663598&req=5

nutrients-07-05470-f002: Study scheme outlining the recruitment and projected incidence of celiac disease (CD) and related HLA genotypes for participants in the Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic Study.
Mentions: Our power assumptions (Figure 2) are based on our recently published data [5,6]. Assuming that: (a) 500 infants will be enrolled during the pilot period and that the drop rate will be no more than 20% given the duration of the study and similar to that we had with our previous studies, [5,6] 400 infants will complete the pilot protocol; (b) the expected probability of CD serum auto antibodies positivity at 18–24 months in first-degree relatives is 10% irrespective of the HLA compatibility; (c) 70% of first degree relatives are HLA DQ2 and/or DQ8 positive (based on our preliminary data); (d) based on points a and b, the expected probability of CD serum auto antibody positivity at 18–24 months in HLA-compatible first degree relatives is 13.3%; (e) the minimal detectable change in CD autoimmunity probability is 10%, we anticipate that during the study period approximately 50 infants will develop CD.

Bottom Line: Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli.These include birthing delivery mode, infant feeding, and antibiotic use.Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

View Article: PubMed Central - PubMed

Affiliation: Center for Celiac Research, Massachusetts General Hospital for Children, Boston, MA 02114, USA. mleonard7@mgh.harvard.edu.

ABSTRACT
In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

No MeSH data available.


Related in: MedlinePlus