{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:11:10Z","timestamp":1782990670191,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Eusko Jaurlaritza","doi-asserted-by":"publisher","award":["GVSAN2018111086, GVSAN2019111085, GVSAN2020111043, IT1739-22"],"award-info":[{"award-number":["GVSAN2018111086, GVSAN2019111085, GVSAN2020111043, IT1739-22"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-106382RB-I00"],"award-info":[{"award-number":["PID2019-106382RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/0149"],"award-info":[{"award-number":["PI21\/0149"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["2021-000007-01EXTF-00209"],"award-info":[{"award-number":["2021-000007-01EXTF-00209"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified several bacteria from <jats:italic>Ruminococcaceae<\/jats:italic> and <jats:italic>Lachnospiraceae<\/jats:italic> families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of <jats:italic>Veillonellaceae<\/jats:italic> family might be causal in the development of CeD, while alterations in <jats:italic>Pasteurellaceae<\/jats:italic> family might be a consequence of the disease itself.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1082862","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T11:59:54Z","timestamp":1688126394000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk"],"prefix":"10.3389","volume":"14","author":[{"given":"B\u00e1rbara 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