An atlas of robust microbiome associations with phenotypic traits based on large-scale cohorts from two continents

PLoS One. 2022 Mar 24;17(3):e0265756. doi: 10.1371/journal.pone.0265756. eCollection 2022.

Abstract

Numerous human conditions are associated with the microbiome, yet studies are inconsistent as to the magnitude of the associations and the bacteria involved, likely reflecting insufficiently employed sample sizes. Here, we collected diverse phenotypes and gut microbiota from 34,057 individuals from Israel and the U.S.. Analyzing these data using a much-expanded microbial genomes set, we derive an atlas of robust and numerous unreported associations between bacteria and physiological human traits, which we show to replicate in cohorts from both continents. Using machine learning models trained on microbiome data, we show prediction accuracy of human traits across two continents. Subsampling our cohort to smaller cohort sizes yielded highly variable models and thus sensitivity to the selected cohort, underscoring the utility of large cohorts and possibly explaining the source of discrepancies across studies. Finally, many of our prediction models saturate at these numbers of individuals, suggesting that similar analyses on larger cohorts may not further improve these predictions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Cohort Studies
  • Gastrointestinal Microbiome* / genetics
  • Humans
  • Microbiota* / genetics
  • Phenotype

Grants and funding

The funders of this study are the European Research Council 786344 and the Israel Science Foundation 292/20. The rest of E.S. support in general but not directly for this project. Daytwo Ltd. provided support for this study in the form of salaries for A.H. and Y.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.