A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determ...

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Published in:Nutrients 2020-05, Vol.12 (5), p.1420
Main Authors: García-Santisteban, Iraia, Cilleros-Portet, Ariadna, Moyua-Ormazabal, Elisabet, Kurilshikov, Alexander, Zhernakova, Alexandra, Garcia-Etxebarria, Koldo, Fernandez-Jimenez, Nora, Bilbao, Jose Ramon
Format: Article
Language:English
Subjects:
celiac disease
Celiac Disease - genetics
Celiac Disease - microbiology
Gastrointestinal Microbiome - genetics
Genetic Predisposition to Disease - epidemiology
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
gut microbiota
Humans
Mendelian randomization
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide - genetics
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Summary:Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculated that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a two-sample Mendelian randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous genome-wide association study (GWAS) of gut microbiota and outcome data from summary statistics of CeD GWAS and Immunochip studies. We identified a number of putative associations between gut microbiota single nucleotide polymorphisms (SNPs) associated with CeD. Regarding bacterial composition, most of the associated SNPs were related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we linked a number of SNPs to several bacterial metabolic pathways that seemed to be related to CeD. Overall, this study represented the first 2SMR approach to elucidate the relationship between microbiome and CeD.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu12051420