A111 ANALYSIS OF GUT MICROBIOME OF HEALTHY INDIVIDUALS THAT GO ON TO DEVELOP CELIAC DISEASE

Abstract

Background

Celiac disease (CeD) is characterized by inflammation of the small intestine due to an intolerance to the gliadin fraction of gluten. Studies have identified a strong genetic component with disease. Several genetic variants have been located within genes of the HLA region, in fact, 85–95% of CeD subjects carry at least one variant of the HLA-DQ2 and/or HLA-DQ8 allele.However, carriers of these variant do not necessarilydevelop the disease. Indeed, although about 40% of the general population are thought to carry the HLA risk allele, only 2–5 % of healthy carriers will develop CeD over time. Recent findings suggest that the microbiota is a contributing factor toward the onset of CeD, however no preexiting celiac microbial signature has been identified.

Aims

In this study, we assess the pre-disease fecal microbiome composition of CeD patients.

Methods

As part of the ongoing GEM Project, we identified 15 subjects who self reported developing CeD. The diagnosis of CeD was supported by the presence of at least one genetic variant associated with CeD. Genotyping was performed using the HumanCoreEXOME chip and imputed to the 1KG genome imputation panel. Seven subjects had bacterial 16S rDNA from stool sequenced using MiSeq Illumina platform after amplification of the V4 hypervariable region. Closed reference operational taxonomic unit picking was performed against GreenGenes database (v 13_8) using QIIME (v1.9) pipeline.Four controls matched for Age, gender, and DQ2.2, DQ2.5, DQ4, and DQ8 allele. The relative abundanceof 230 taxa were compared using a conditional logistic regression. Covariates of the model included total number of reads per sample.

Results

Relative abundance of the genus Coprococcus and of an unknown genus of the Peptostreptococcacae family were higher in the CeD individuals (p <0.05). Alpha diversity, as assessed by the Shannon index was similar between the two groups.

Conclusions

These findings suggest an increase in Coprococcus and of an unknown genus of the Peptostreptococcacae family in prediseasesamples of CeD patients, although the p values did not survive correction for multiple testing. The potential implication of these difference remain to be confirmed but suggest the possibility of a microbiome driven initiation of disease.

Submitted on behalf of behalf of the CCC IBD GEM Project research team.

Funding Agencies

CCC, CIHR