Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany; email:
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Annu Rev Genet. 2017 Nov 27;51:413-433. doi: 10.1146/annurev-genet-110711-155532. Epub 2017 Sep 20.
The body's microbiome, composed of microbial cells that number in the trillions, is involved in human health and disease in ways that are just starting to emerge. The microbiome is assembled at birth, develops with its host, and is greatly influenced by environmental factors such as diet and other exposures. Recently, a role for human genetic variation has emerged as also influential in accounting for interpersonal differences in microbiomes. Thus, human genes may influence health directly or by promoting a beneficial microbiome. Studies of the heritability of gut microbiotas reveal a subset of microbes whose abundances are partly genetically determined by the host. However, the use of genome-wide association studies (GWASs) to identify human genetic variants associated with microbiome phenotypes has proven challenging. Studies to date are small by GWAS standards, and cross-study comparisons are hampered by differences in analytical approaches. Nevertheless, associations between microbes or microbial genes and human genes have emerged that are consistent between human populations. Most notably, higher levels of beneficial gut bacteria called Bifidobacteria are associated with the human lactase nonpersister genotype, which typically confers lactose intolerance, in several different human populations. It is time for the microbiome to be incorporated into studies that quantify interactions among genotype, environment, and the microbiome in order to predict human disease susceptibility.
人体微生物组由数量达到万亿的微生物细胞组成，其在人类健康和疾病方面的作用才刚刚开始显现。微生物组在出生时就已形成，随着宿主而发展，并受饮食和其他暴露等环境因素的极大影响。最近，人类遗传变异的作用也被认为对微生物组个体间差异有影响。因此，人类基因可能通过促进有益的微生物组直接或间接地影响健康。对肠道微生物组遗传力的研究揭示了一部分微生物的丰度部分由宿主的遗传决定。然而，使用全基因组关联研究（GWAS）来识别与微生物组表型相关的人类遗传变异一直具有挑战性。迄今为止的研究按 GWAS 标准来看规模较小，并且由于分析方法的差异，跨研究比较受到阻碍。尽管如此，在人类群体中，微生物或微生物基因与人类基因之间的关联已经出现，并且是一致的。最值得注意的是，在几个不同的人类群体中，被称为双歧杆菌的有益肠道细菌数量较多与人类乳糖酶非持续存在基因型有关，这种基因型通常会导致乳糖不耐受。现在是时候将微生物组纳入研究中，以定量评估基因型、环境和微生物组之间的相互作用，从而预测人类疾病易感性了。
