Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk
dc.contributor.author | González García, Bárbara P. | |
dc.contributor.author | Marí Alemany, Sergi | |
dc.contributor.author | Cilleros Portet, Ariadna ![]() | |
dc.contributor.author | Hernangómez Laderas, Alba | |
dc.contributor.author | Fernández Jiménez, Nora ![]() | |
dc.contributor.author | García Santisteban, Iraia ![]() | |
dc.contributor.author | Bilbao Catalá, José Ramón ![]() | |
dc.date.accessioned | 2024-05-23T17:05:41Z | |
dc.date.available | 2024-05-23T17:05:41Z | |
dc.date.issued | 2023-06 | |
dc.identifier.citation | Frontiers in Immunology 14 : (2023) // Article ID 1082862 | es_ES |
dc.identifier.issn | 1664-3224 | |
dc.identifier.uri | http://hdl.handle.net/10810/68127 | |
dc.description.abstract | Background: Celiac Disease (CeD) is an autoimmune disorder triggered by gluten intake in genetically susceptible individuals. Highest risk individuals are homozygous for the Human Leucocyte Antigen (HLA) DQ2.5 haplotype or DQ2.5/DQ2.2 heterozygous. Both the HLA-DQ2-positive high genetic risk individuals and those that have developed the disease have altered intestinal microbiota, but it remains unclear whether these alterations are a cause or a consequence of CeD. Objective: To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals. Materials and Methods: We performed a bidirectional Two-Sample Mendelian Randomization (2SMR) test using summary statistics from the largest publicly available Genome-Wide Association Study (GWAS) of GM and the summary statistics of the Immunochip CeD study of those individuals with the HLA-DQ2 high-risk haplotype. To test whether changes in GM composition were causally linked to CeD, GM data were used as exposure and CeD data as outcome; to test for reverse causation, the exposure and outcome datasets were inverted. Results: We identified several bacteria from Ruminococcaceae and Lachnospiraceae families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of Veillonellaceae family might be causal in the development of CeD, while alterations in Pasteurellaceae family might be a consequence of the disease itself. Conclusion: Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional. | es_ES |
dc.description.sponsorship | Funding for the project was provided by the Wellcome Trust under awards 076113, 085475, and 099355. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Frontiers Media | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Mendelian randomization | es_ES |
dc.subject | celiac disease | es_ES |
dc.subject | HLA-DQ2 | es_ES |
dc.subject | gut microbiota | es_ES |
dc.subject | bidirectional causality | es_ES |
dc.title | Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2023 González-García, Marí, Cilleros-Portet, Hernangomez-Laderas, Fernandez-Jimenez, García-Santisteban and Bilbao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1082862/full | es_ES |
dc.identifier.doi | 10.3389/fimmu.2023.1082862 | |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoes | Pediatría | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |
dc.departamentoeu | Pediatria | es_ES |
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Except where otherwise noted, this item's license is described as © 2023 González-García, Marí, Cilleros-Portet, Hernangomez-Laderas, Fernandez-Jimenez, García-Santisteban and Bilbao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.