Schmidt Victor, Enav Hagay, Spector Timothy D, Youngblut Nicholas D, Ley Ruth E
Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom.
mSystems. 2020 Sep 29;5(5):e00911-20. doi: 10.1128/mSystems.00911-20.
One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of in adults with lactase gene () single nucleotide polymorphisms (SNPs) associated with lactase nonpersistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer-grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with various lactase persistence genotypes. We further employed a novel genome-capture-based enrichment of DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. and were the most abundant species regardless of host genotype. genotypes could not be discriminated based on relative abundances of species or community structure. Three distinct metagenomic analysis methods of -enriched DNA revealed intraindividual temporal stability of , , and strains against the background of a changeable microbiome. Two of our three methods also observed greater strain sharing within MZ twin pairs than within unrelated individuals for , while no method revealed an effect of host genotype on strain composition. Our results support a "rising tide lifts all boats" model for the dominant bifidobacteria in the adult gut: their higher abundance in lactase-nonpersistent than in lactase-persistent individuals results from an expansion at the genus level. species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood. When humans domesticated animals, some adapted genetically to digest milk into adulthood (lactase persistence). The gut microbiomes of people with lactase-persistent genotypes (AA or AG) differ from those with lactase-nonpersistent genotypes (GG) by containing fewer bacteria belonging to the bifidobacteria, a group which contains beneficial species. Here, we asked if the gut microbiomes of adults with GG and AA/AG genotypes differ in the species of bifidobacteria present. In particular, we used a novel technique which allowed us to compare bifidobacteria in adults at the strain level, without the traditional need for culturing. Our results show that the GG genotype enhances the abundance of bifidobacteria regardless of species. We also noted that a person's specific strains are recoverable several years later, and twins can share the same ones. Given that bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long-term, multigenerational inheritance.
人类遗传学与肠道微生物群之间最显著的关联之一是，与乳糖酶持续性（AA/AG基因型）相比，乳糖酶基因（）单核苷酸多态性（SNP）与乳糖酶不持续性（GG基因型）相关的成年人中， 的相对丰度更高。为了更精细地解析这种关联的系统发育关系，我们研究了来自具有不同乳糖酶持续性基因型的成年人肠道微生物群的1680个16S rRNA文库和245个宏基因组。我们进一步采用了一种基于基因组捕获的新方法，从这些宏基因组的一个子集中富集 DNA，包括同卵（MZ）双胞胎对，每个双胞胎对采集2或3次样本。无论宿主 基因型如何， 和 都是最丰富的 物种。无法根据 物种的相对丰度或 群落结构来区分 基因型。三种不同的宏基因组分析方法对富集的 DNA进行分析，结果显示在不断变化的微生物群背景下， 、 和 菌株在个体内部具有时间稳定性。我们的三种方法中有两种还观察到，与无关个体相比，MZ双胞胎对中 的菌株共享性更高，而没有一种方法显示宿主 基因型对 菌株组成有影响。我们的结果支持了成年肠道中占主导地位的双歧杆菌的“水涨船高”模型：它们在乳糖酶不持续性个体中的丰度高于乳糖酶持续性个体，这是由于在属水平上的扩张。已知 物种是从母亲传给孩子的，并且在婴儿期和儿童期个体内部是稳定的：我们的结果将这种稳定性扩展到了成年期。当人类驯化动物时，一些人在基因上适应了成年后消化牛奶（乳糖酶持续性）。乳糖酶持续性基因型（AA或AG）的人的肠道微生物群与乳糖酶不持续性基因型（GG）的人的肠道微生物群不同，前者含有较少属于双歧杆菌的细菌，双歧杆菌是一个包含有益物种的菌群。在这里，我们询问了GG和AA/AG基因型的成年人肠道微生物群中存在的双歧杆菌物种是否不同。特别是，我们使用了一种新技术，使我们能够在菌株水平上比较成年人中的双歧杆菌，而无需传统的培养。我们的结果表明，无论物种如何，GG基因型都会提高双歧杆菌的丰度。我们还注意到，一个人的特定菌株在几年后仍可恢复，双胞胎可以共享相同的菌株。鉴于双歧杆菌是从母亲传给孩子的，成年期随时间的菌株稳定性表明存在长期的多代遗传。
