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Article

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

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Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Spain
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Department of Genetics, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
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Biodonostia, Gastrointestinal genetics group, 20014 San Sebastian, Spain
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Spanish Biomedical Research Center in Liver and Digestive Diseases, CIBERehd, 28029 Madrid, Spain
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Spanish Biomedical Research Center in Diabetes and associated Metabolic Disorders, CIBERDEM, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Nutrients 2020, 12(5), 1420; https://doi.org/10.3390/nu12051420
Received: 24 March 2020 / Revised: 5 May 2020 / Accepted: 11 May 2020 / Published: 14 May 2020
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. View Full-Text
Keywords: celiac disease; gut microbiota; Mendelian randomization celiac disease; gut microbiota; Mendelian randomization
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MDPI and ACS Style

García-Santisteban, I.; Cilleros-Portet, A.; Moyua-Ormazabal, E.; Kurilshikov, A.; Zhernakova, A.; Garcia-Etxebarria, K.; Fernandez-Jimenez, N.; Bilbao, J.R. A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease. Nutrients 2020, 12, 1420. https://doi.org/10.3390/nu12051420

AMA Style

García-Santisteban I, Cilleros-Portet A, Moyua-Ormazabal E, Kurilshikov A, Zhernakova A, Garcia-Etxebarria K, Fernandez-Jimenez N, Bilbao JR. A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease. Nutrients. 2020; 12(5):1420. https://doi.org/10.3390/nu12051420

Chicago/Turabian Style

García-Santisteban, Iraia, Ariadna Cilleros-Portet, Elisabet Moyua-Ormazabal, Alexander Kurilshikov, Alexandra Zhernakova, Koldo Garcia-Etxebarria, Nora Fernandez-Jimenez, and Jose R. Bilbao 2020. "A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease" Nutrients 12, no. 5: 1420. https://doi.org/10.3390/nu12051420

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