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Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease

Paolo Manghi, Giacomo Antonello, L. Schiffer, Davide Golzato, Andres Wokaty, F. Beghini, C. Mirzayi, Kaelyn Long et al.

Nature Communications, 2025

24 citations

Abstract

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. Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

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