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Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.<\/jats:p>","DOI":"10.1126\/scitranslmed.abk0855","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T17:56:36Z","timestamp":1654710996000},"source":"Crossref","is-referenced-by-count":147,"title":["Risk assessment with gut microbiome and metabolite markers in NAFLD development"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-480X","authenticated-orcid":true,"given":"Howell","family":"Leung","sequence":"first","affiliation":[{"name":"Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute, Beutenbergstra\u00dfe 11A, 07745 Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-8422","authenticated-orcid":true,"given":"Xiaoxue","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-7354","authenticated-orcid":true,"given":"Yueqiong","family":"Ni","sequence":"additional","affiliation":[{"name":"Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute, Beutenbergstra\u00dfe 11A, 07745 Jena, Germany."},{"name":"Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1306-683X","authenticated-orcid":true,"given":"Emmanouil","family":"Nychas","sequence":"additional","affiliation":[{"name":"Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute, Beutenbergstra\u00dfe 11A, 07745 Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-3962","authenticated-orcid":true,"given":"Sara Leal","family":"Siliceo","sequence":"additional","affiliation":[{"name":"Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology\u2013Hans Kn\u00f6ll Institute, Beutenbergstra\u00dfe 11A, 07745 Jena, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-9263","authenticated-orcid":true,"given":"Dennis","family":"Pohl","sequence":"additional","affiliation":[{"name":"Clinical Microbiomics, Fruebjergvej 3, 2100 Copenhagen, Denmark."},{"name":"Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Building 220, 2800 Kgs. 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