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

Petar Scepanovic,The Milieu Intérieur Consortium ,Christian Hammer,Stanislas Mondot,Allyson Byrd,Etienne Patin,Flavia Hodel,Darragh Duffy,Olivier Lantz,Valentin Partula,Mathilde Touvier,Jacques Fellay,Cécile Alanio,Lluis Quintana-Murci,Jacob Bergstedt,Matthew L Albert

doi:10.1186/s40168-019-0747-x

Abstract

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

Highlights

The gut microbiome is an important determinant of human health
Gut microbiome diversity in healthy donors To characterize the bacterial diversity of the gut flora of the 1000 healthy donors, we performed 16S ribosomal RNA (rRNA) gene sequencing on standardized collections of fecal samples
We identified variables associated with overall microbiome composition and with a small number of individual taxa, explaining a non-negligible fraction of microbiome diversity in healthy individuals in the absence of drug treatment

Summary

Introduction

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. A wide diversity of microbial species colonizes the human body, providing considerable benefits to the host through a range of different functions [1]. These microbes generate metabolites that can act as energy sources for cell metabolism, promote the development and the functionality of the immune system, and prevent colonization by pathogenic microorganisms [2]. Multiple 16S ribosomal RNA (rRNA) gene sequencing and metagenomic studies established that each individual gut microbiome harbors a unique combination of microbial life [3, 4]. The human gut microbiome is dominated by five bacterial phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia [6, 7]. The microbiome composition evolves rapidly during the first 3 years of life, followed by a more gradual maturation [11], and is predicted to remain relatively stable throughout adult life [12]

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