The composition of the gut microbiome is impacted by a complex array of factors, from nutrient composition and availability, to physical factors like temperature, pH, and flow rate, as well as interactions among the members of the microbial community. Many of these factors are affected by the host, raising the question of how host genetic variation impacts microbiome composition. Though human studies confirm this type of role for host genetics, its overall importance is still a subject of debate and remains difficult to study. The mouse model, by allowing the strict control of genetics, nutrition, and other environmental factors, has provided an excellent opportunity to extend this work, and the Diversity Outbred (DO) mice in particular present a chance to pinpoint host genetic variants that influence microbiome composition at different levels of generality. Here, we apply 16S rRNA gene sequencing to fecal samples of 247 DO male mice to estimate heritability and perform taxon-specific QTL mapping of microbial relative abundances revealing an increasingly heterogeneous picture of host function and microbial taxa at the host-microbiome interface. We present the first report of significant heritability of phylum Tenericutes in mice, and find novel QTL-spanning genes involved in antibacterial pathways, immune and inflammatory disease, and lipid metabolism.

中文翻译：

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利用多样性近交小鼠进行的高分辨率QTL定位可以鉴定影响肠道微生物组组成的遗传变异

肠道微生物组的组成会受到一系列复杂因素的影响，这些因素包括营养成分和可利用性，以及诸如温度，pH和流速等物理因素，以及微生物群落成员之间的相互作用。这些因素中有许多受宿主影响，这就提出了宿主遗传变异如何影响微生物组组成的问题。尽管人类研究证实了宿主遗传学的这种作用，但其总体重要性仍是一个争论的话题，并且仍然难以研究。通过严格控制遗传，营养和其他环境因素，小鼠模型为扩展这项工作提供了绝佳的机会，尤其是多样性近交（DO）小鼠提供了一个机会，可以在不同的普遍性水平上确定影响微生物组组成的宿主遗传变异。在这里，我们对247只DO雄性小鼠的粪便样本应用16S rRNA基因测序，以评估遗传力并进行微生物相对丰度的分类群特异性QTL定位，揭示宿主-微生物组界面上宿主功能和微生物分类群的异质性越来越高。我们目前在小鼠中显着遗传门球菌的遗传力的第一份报告，并发现涉及抗菌途径，免疫和炎性疾病以及脂质代谢的新型QTL跨越基因。我们对247只DO雄性小鼠的粪便样品应用16S rRNA基因测序，以评估遗传力，并对微生物相对丰度进行分类群特异性QTL定位，揭示宿主-微生物组界面上宿主功能和微生物分类群的异质性越来越高。我们目前在小鼠中显着遗传门球菌的遗传力的第一份报告，并发现涉及抗菌途径，免疫和炎性疾病以及脂质代谢的新型QTL跨越基因。我们对247只DO雄性小鼠的粪便样品应用16S rRNA基因测序，以评估遗传力，并对微生物相对丰度进行分类群特异性QTL定位，揭示宿主-微生物组界面上宿主功能和微生物分类群的异质性越来越高。我们目前在小鼠中显着遗传门球菌的遗传力的第一份报告，并发现涉及抗菌途径，免疫和炎性疾病以及脂质代谢的新型QTL跨越基因。