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Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore. Microbial abundance profiles were estimated using ensembles of Kaiju, Kraken2, and DeepMicrobes calls followed by dimensionality reduction. The area under the curve (AUC) was used to evaluate classification of the samples (aGvHD vs. none) using an elastic net to test the relevance of metagenomic data. Clinical data included the underlying disease (leukemia vs. other hematological malignancies), recipient age, and sex. Among 172 aHSCT patients of whom 42 developed aGVHD post transplantation, a total of 181 pre-transplant tool samples were analyzed. The top performing model predicting risk of aGVHD included a reduced species profile (AUC = 0.672). Beta diversity (37% in Jaccard\u2019s Nestedness by mean fold change, p &lt; 0.05) was lower in those developing aGvHD. Ten bacterial species including Prevotella and Eggerthella genera were consistently found to associate with aGvHD in indicator species analysis, as well as relief and impurity-based algorithms. The findings support the hypothesis on potential associations between gut microbiota and aGvHD based on a data-driven approach to MWAS. This highlights the need and relevance of routine stool collection for the discovery of novel biomarkers.<\/jats:p>","DOI":"10.3390\/cells11244089","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T07:27:30Z","timestamp":1671434850000},"page":"4089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-1656","authenticated-orcid":false,"given":"Ramtin","family":"Zargari Marandi","sequence":"first","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2804-0560","authenticated-orcid":false,"given":"Mette","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Elizabeth","family":"Ilett","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Christian","family":"N\u00f8rgaard","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-1395","authenticated-orcid":false,"given":"Marc","family":"Noguera-Julian","sequence":"additional","affiliation":[{"name":"IrsiCaixa Institute for AIDS Research, 08916 Badalona, Catalonia, Spain"},{"name":"Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic\u2014Central University of Catalonia (UVic\u2014UCC), 08500 Vic, Spain"},{"name":"Infectious Disease Networking Biomedical Research Center, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Paredes","sequence":"additional","affiliation":[{"name":"IrsiCaixa Institute for AIDS Research, 08916 Badalona, Catalonia, Spain"},{"name":"Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic\u2014Central University of Catalonia (UVic\u2014UCC), 08500 Vic, Spain"},{"name":"Infectious Disease Networking Biomedical Research Center, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens D.","family":"Lundgren","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark"},{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Sengel\u00f8v","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, 2200 Copenhagen, Denmark"},{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-9736","authenticated-orcid":false,"given":"Cameron Ross","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1750-1172-2-35","article-title":"Acute Graft versus Host Disease","volume":"2","author":"Jacobsohn","year":"2007","journal-title":"Orphanet J. 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