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In this cross-sectional study that accounted for clinical covariates and dietary intake, we compared the taxonomic composition and gut microbial function in a cohort of 164 cognitively normal individuals, 49 of whom showed biomarker evidence of early preclinical AD. Gut microbial taxonomic profiles of individuals with preclinical AD were distinct from those of individuals without evidence of preclinical AD. The change in gut microbiome composition correlated with \u03b2-amyloid (A\u03b2) and tau pathological biomarkers but not with biomarkers of neurodegeneration, suggesting that the gut microbiome may change early in the disease process. We identified specific gut bacterial taxa associated with preclinical AD. Inclusion of these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status when tested on a subset of the cohort (65 of the 164 participants). Gut microbiome correlates of preclinical AD neuropathology may improve our understanding of AD etiology and may help to identify gut-derived markers of AD risk.<\/jats:p>","DOI":"10.1126\/scitranslmed.abo2984","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T13:58:28Z","timestamp":1686751108000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":375,"title":["Gut microbiome composition may be an indicator of preclinical Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-2460","authenticated-orcid":true,"given":"Aura L.","family":"Ferreiro","sequence":"first","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Biomedical Engineering, Washington University in St.\u00a0Louis, St.\u00a0Louis, MO 63130, USA."},{"name":"Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-2470","authenticated-orcid":true,"given":"JooHee","family":"Choi","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-4521","authenticated-orcid":true,"given":"Jian","family":"Ryou","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-0359","authenticated-orcid":true,"given":"Erin P.","family":"Newcomer","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Biomedical Engineering, Washington University in St.\u00a0Louis, St.\u00a0Louis, MO 63130, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-2581","authenticated-orcid":true,"given":"Regina","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-8372","authenticated-orcid":true,"given":"Rebecca M.","family":"Bollinger","sequence":"additional","affiliation":[{"name":"Program in Occupational Therapy, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Hall-Moore","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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