A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals

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BACKGROUND: The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. RESULTS: Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. CONCLUSION: In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01699893.


  • Petar Scepanovic
  • Flavia Hodel
  • Stanislas Mondot
  • Valentin Partula
  • Allyson Byrd
  • Christian Hammer
  • Cécile Alanio
  • Jacob Bergstedt
  • Etienne Patin
  • Mathilde Touvier
  • Olivier Lantz
  • Matthew L. Albert
  • Darragh Duffy
  • Lluis Quintana-Murci
  • Jacques Fellay
  • Milieu Intérieur Consortium
Enheter & grupper
Externa organisationer
  • Swiss Federal Institute of Technology
  • Swiss Institute of Bioinformatics
  • INRA National Institute of Agricultural Research
  • Centre of Epidemiology And Biostatistics Sorbonne Paris Cité Center (CRESS)
  • Genentech, Inc
  • University of Pennsylvania
  • Pasteur Institute
  • Lausanne University Hospital
  • Paris Diderot University
  • Centre National de la Recherche Scientifique (CNRS)
  • Curie Institute, Paris

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
  • Medicinsk genetik


Antal sidor1
Utgåva nummer1
StatusPublished - 2019 sep 13
Peer review utfördJa