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.

中文翻译：

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对人口、环境和宿主遗传与健康个体肠道微生物组多样性的关联进行全面评估。

背景肠道微生物组是人类健康的重要决定因素。它的组成已被证明受到多种环境因素的影响，并可能受到宿主遗传变异的影响。在Milieu Intérieur Consortium的框架内，总共招募了1000名西欧血统的健康个体，性别比例为1:1，并且在5个十年的生命中（20-69岁）均匀分层。我们从 858 名参与者的粪便样本中生成了 16S 核糖体 RNA 谱。我们研究了导致粪便微生物组组成个体差异的遗传和非遗传因素。结果 在 110 个人口、临床和环境因素中，有 11 个被确定与多变量模型中特定微生物群落的 α 多样性、β 多样性或丰度显着相关。年龄和血液丙氨酸转氨酶水平与微生物组多样性的关联最强。总的来说，所有非遗传因素解释了 16.4% 的差异。然后，我们搜索了超过 500 万个单核苷酸多态性与粪便微生物组多样性的相同指标之间的关联，包括作为协变量的重要非遗传因素。经过多次测试校正后，没有发现全基因组的显着关联。之前报道的人类遗传变异和特定分类单元之间的一小部分关联可以在我们的队列中复制，而任何多样性指标都没有观察到复制。结论 在一个特征明确的健康个体队列中，我们确定了几个与粪便微生物组多样性相关的非遗传变量。相比之下，宿主遗传学的影响可以忽略不计。因此，人口和环境因素是健康个体粪便微生物组组成的主要影响因素。试验注册 ClinicalTrials.gov 标识符 NCT01699893。