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

Microbiome

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[1] 0000 0001 0930 2361, grid.4514.4, Department of Automatic Control, LTH, Lund University, Lund, Sweden;0000 0001 2353 6535, grid.428999.7, Unit of Human Evolutionary Genetics, Department of Genomes and Genetics, Institut Pasteur, Paris, France;0000 0001 2112 9282, grid.4444.0, Centre National de la Recherche Scientifique, UMR2000, Paris, France;0000 0004 0522 0627, grid.462293.8, MICALIS Institute (INRA/AgroParisTech), Jouy-en-Josas, France;0000 0004 0534 4718, grid.418158.1, Department of Cancer Immunology, Genentech Inc., 94080, San Francisco, CA, USA;0000 0004 0534 4718, grid.418158.1, Department of Cancer Immunology, Genentech Inc., 94080, San Francisco, CA, USA;0000 0004 0534 4718, grid.418158.1, Department of Human Genetics, Genentech Inc., 94080, San Francisco, CA, USA;0000 0004 0639 6384, grid.418596.7, Institut Curie, PSL Research University, Inserm U932, 75005, Paris, France;Center of Clinical Investigations, CICBT1428 IGR/Curie, 75005, Paris, France;0000 0004 1936 8972, grid.25879.31, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;0000000121839049, grid.5333.6, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;0000 0001 2223 3006, grid.419765.8, Swiss Institute of Bioinformatics, Lausanne, Switzerland;0000000121839049, grid.5333.6, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;0000 0001 2223 3006, grid.419765.8, Swiss Institute of Bioinformatics, Lausanne, Switzerland;0000 0001 0423 4662, grid.8515.9, Precision Medicine Unit, Lausanne University Hospital, Lausanne, Switzerland;0000000121866389, grid.7429.8, Immunobiology of Dendritic Cells laboratory (INSERM U1223/Institut Pasteur), Paris, France;Sorbonne-Paris-Cité Research Center for Epidemiology and Statistics CRESS, Nutritional Epidemiology Research Team EREN (INSERM U1153/INRA U1125/CNAM/Université Paris-XIII Nord), Bobigny, France;Sorbonne-Paris-Cité Research Center for Epidemiology and Statistics CRESS, Nutritional Epidemiology Research Team EREN (INSERM U1153/INRA U1125/CNAM/Université Paris-XIII Nord), Bobigny, France;0000 0001 2217 0017, grid.7452.4, University of Paris-VII Denis Diderot, Sorbonne-Paris-Cité University, Paris, France;

关键词: Microbiome;    Gut;    Human;    Genomics;    16S rRNA gene sequencing;    GWAS;    Healthy;    Demographics;    Environment;   

DOI  :  10.1186/s40168-019-0747-x

来源: publisher

【 摘 要 】

BackgroundThe 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.ResultsAmong 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.ConclusionIn 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 registrationClinicalTrials.gov identifier NCT01699893

【 授权许可】

CC BY