Department of Food Science and Technology and Core for Applied Genomics and Ecology, University of Nebraska, Lincoln, NE 68583-0919, USA.
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18933-8. doi: 10.1073/pnas.1007028107. Epub 2010 Oct 11.
In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.
在包括人类在内的脊椎动物中，个体体内存在着肠道微生物群落，其物种组成和优势微生物群体的相对比例存在着巨大的差异。尽管外部和随机因素显然对微生物组的个体性有贡献，但决定环境因素和宿主遗传因素如何结合来塑造这个复杂生态系统的基本原理在很大程度上是未知的，需要系统的研究。在这里，我们研究了影响源自 C57BL/6J 和 ICR 衍生的远交系（HR）杂交的一个大型（n = 645）小鼠高级近交系（AIL）中微生物组组成的因素。对微生物组进行定量焦磷酸测序，定义了一个核心可测量的微生物组（CMM），其中包含 64 个保守的分类群，在该种群中的大多数动物中都存在数量上的变化。尽管这种变化的一部分可以用窝和群体效应来解释，但个体宿主基因型也有一定的贡献。对与 530 个完全信息 SNP 标记的 CMM 丰度进行共分离测试，确定了 18 个宿主数量性状基因座（QTL），这些 QTL 与特定微生物类群的相对丰度存在显著或提示性的全基因组连锁。这些 QTL 通过三种方式影响微生物组的组成；一些位点控制单个微生物物种，一些控制相关类群的集合，一些对远缘相关生物的集合具有潜在的多效性效应。这些数据为宿主遗传控制在塑造哺乳动物个体微生物组多样性方面的重要性提供了明确的证据，这是理解控制与复杂疾病相关的肠道微生物群组合的因素的关键一步。
