Symbiotic relationships between hosts and microorganisms remain to be fully understood from a genetic perspective. Zhernakova et al. carried out a genome-wide association meta-analysis of human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts: the Dutch Microbiome Project, Lifelines-DEEP, the 500 Functional Genomics Project and 300-Obesity. The study identified genome-wide associations of human single-nucleotide polymorphisms (SNPs) and gut microbial structural variations. Notably, a strong association was found between the human ABO-encoded A blood group and a structural variation segment in Faecalibacterium prausnitzii harboring an N-acetylgalactosamine (GalNAc) metabolism gene cluster, which was replicated in a Tanzanian cohort. Further bioinformatics and experimental validation demonstrated that other ABO-associated species can also utilize GalNAc. Comparison of GalNAc associations between two groups of individuals suggested that the abundance of GalNAc genes might be more relevant for host health in individuals with mucosal A-antigens than for those without. The results shed light on human genetic regulation of the genetic diversity of gut microorganisms, and will hopefully enhance our understanding of the crosstalk between the human genome and the microbial metagenome.

Original reference: Nature 625, 813–821 (2024)

从遗传学角度来看，宿主和微生物之间的共生关系仍有待充分理解。热尔纳科娃等人。对来自四个荷兰队列的 9,015 名个体进行了人类遗传变异和肠道微生物结构变异的全基因组关联荟萃分析：荷兰微生物组计划、生命线-DEEP、500 功能基因组计划和 300-肥胖。该研究确定了人类单核苷酸多态性 (SNP) 和肠道微生物结构变异的全基因组关联。值得注意的是，人类ABO编码的 A 血型与含有N-乙酰半乳糖胺 (GalNAc) 代谢基因簇的普氏粪杆菌的结构变异片段之间发现了很强的关联，该基因簇在坦桑尼亚队列中得到了复制。进一步的生物信息学和实验验证表明其他ABO相关物种也可以利用 GalNAc。两组个体之间 GalNAc 关联的比较表明，与没有粘膜 A 抗原的个体相比，GalNAc 基因的丰度可能与具有粘膜 A 抗原的个体的宿主健康更相关。这些结果揭示了人类对肠道微生物遗传多样性的遗传调控，并有望增强我们对人类基因组和微生物宏基因组之间串扰的理解。

原始参考文献： Nature 625 , 813–821 (2024)