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

Scepanovic, Petar ; Hodel, Flavia ; Mondot, Stanislas ; Partula, Valentin ; Byrd, Allyson ; Hammer, Christian ; Alanio, Cécile ; Bergstedt, Jacob LU ; Patin, Etienne and Touvier, Mathilde , et al. (2019) In Microbiome 7(1).
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
16S rRNA gene sequencing, Demographics, Environment, Genomics, Gut, GWAS, Healthy, Human, Microbiome
in
Microbiome
volume
7
issue
1
pages
1 pages
publisher
BioMed Central (BMC)
external identifiers
  • pmid:31519223
  • scopus:85072197664
ISSN
2049-2618
DOI
10.1186/s40168-019-0747-x
language
English
LU publication?
yes
id
ffcde02b-e547-4e05-a954-cb140865f988
date added to LUP
2019-10-01 11:10:28
date last changed
2021-01-19 01:08:18
@article{ffcde02b-e547-4e05-a954-cb140865f988,
  abstract     = {<p>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 &gt; 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.</p>},
  author       = {Scepanovic, Petar and Hodel, Flavia and Mondot, Stanislas and Partula, Valentin and Byrd, Allyson and Hammer, Christian and Alanio, Cécile and Bergstedt, Jacob and Patin, Etienne and Touvier, Mathilde and Lantz, Olivier and Albert, Matthew L. and Duffy, Darragh and Quintana-Murci, Lluis and Fellay, Jacques},
  issn         = {2049-2618},
  language     = {eng},
  month        = {09},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Microbiome},
  title        = {A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals},
  url          = {http://dx.doi.org/10.1186/s40168-019-0747-x},
  doi          = {10.1186/s40168-019-0747-x},
  volume       = {7},
  year         = {2019},
}