Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease
Large public datasets of the human microbiome now exist but combining them for large-scale analysis is difficult due to a lack of standardization. We developed curatedMetagenomicData (cMD) 3, a uniformly processed collection of over 22,000 human microbiome samples with manually curated metadata from 94 studies and 42 countries. This large and diverse resource allows for meta-analysis of the links between microbes and human health. Through meta-analysis, we identified hundreds of microbial species and thousands of microbial functions significantly associated with a person's sex, age, body mass index, and disease status, and catalog these as references. We developed an "oral enrichment score" (OES) based on the relative abundance of bacteria typically found in the oral cavity and not in the gut. Higher OES in the gut is a consistent feature in individuals with disease, suggesting that the relative abundance of oral bacteria in the gut is a simple and quantifiable signal of altered microbiome health. These analyses identify modest but widely shared patterns in human microbiomes, serving as a reproducible and readily updatable reference.
Authors
- Marcel Ramos (ORCID: https://orcid.org/0000-0002-6155-3245)
- Gianmarco Piccinno (ORCID: https://orcid.org/0000-0003-1947-1817)
- Curtis Huttenhower (ORCID: https://orcid.org/0000-0002-1110-0096)
- Anna Pedrotti (ORCID: https://orcid.org/0009-0005-2035-9832)
- Sabrina Tamburini (ORCID: https://orcid.org/0000-0002-2485-7418)
- Paolo Manghi (ORCID: https://orcid.org/0000-0003-0846-6529)
- Shaimaa Elsafoury (ORCID: https://orcid.org/0000-0002-0120-7746)
- Sean M. Davis (ORCID: https://orcid.org/0000-0001-9276-6158)
- Moreno Zolfo (ORCID: https://orcid.org/0000-0001-6661-4046)
- Ludwig Geistlinger (ORCID: https://orcid.org/0000-0002-2495-5464)
- Francesco Asnicar (ORCID: https://orcid.org/0000-0003-3732-1468)
- Lucas Schiffer (ORCID: https://orcid.org/0000-0003-3628-0326)
- Davide Golzato (ORCID: https://orcid.org/0000-0002-2890-1527)
- Kelly B. Eckenrode (ORCID: https://orcid.org/0000-0002-0821-0112)
- Kaelyn Long
- Valentina Giunchiglia (ORCID: https://orcid.org/0000-0002-2165-7840)
- Fatima Zohra (ORCID: https://orcid.org/0000-0002-2205-4929)
- Giacomo Antonello (ORCID: https://orcid.org/0000-0001-7842-0898)
- Levi Waldron (ORCID: https://orcid.org/0000-0003-2725-0694)
- Samuel David Gamboa-Tuz (ORCID: https://orcid.org/0000-0002-6863-7943)
- Blanco-Miguez Aitor
- Ilya Likhotkin
- Nicola Segata (ORCID: https://orcid.org/0000-0002-1583-5794)
- Chloe Mirzayi (ORCID: https://orcid.org/0000-0002-9817-2868)
- Heidi E. Jones (ORCID: https://orcid.org/0000-0002-4285-3752)
- Vincent J. Carey (ORCID: https://orcid.org/0000-0003-4046-0063)
- Mireia Valles‐Colomer (ORCID: https://orcid.org/0000-0002-1988-6054)
- Rimsha Azhar
- Kai Gravel-Pucillo
- M. Keller (ORCID: https://orcid.org/0000-0002-1485-415X)
- Giacomo D’Amato
- Andres Wokaty
- Arianna Bonetti
- Francesco Beghini
- Sehyun Oh
- Andrew Maltez Thomas
- Edoardo Pasolli
Institutions
- Fondazione Edmund Mach (IT)
- Broad Institute (US)
- Boston University (US)
- The Graduate Center, CUNY (US)
- Harvard University (US)
- Colorado School of Public Health (US)
- City University of New York (US)
- University of Trento (IT)
- Heidelberg University (DE)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Imperial College London (GB)
- Mass General Brigham (US)
- University of Colorado Anschutz Medical Campus (US)
- European Institute of Oncology (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-23
- DOI
- https://doi.org/10.1038/s41467-025-66888-1
- Citations
- 5
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- National Institutes of Health
- National Cancer Institute