荷兰格罗宁根大学Jingyuan Fu和Hermie J. M. Harmsen共同合作，近期取得重要工作进展。他们研究发现宿主基因可调控人类肠道微生物结构变异。相关研究成果2024年1月3日在线发表于《自然》杂志上。
据介绍，尽管宿主遗传学对肠道微生物多样性和特定分类群丰度的影响已得到充分证实，但对宿主遗传学如何调节肠道微生物的遗传多样性知之甚少。
研究人员对来自四个荷兰队列的9015名个体的人类基因变异和肠道微生物结构变异之间的关系进行了荟萃分析。在分泌终止于GalNAc的a型寡糖抗原的个体中，携带N-乙酰氨基半乳糖（GalNAc）利用基因簇的prausnitzii粪杆菌中结构变异片段的存在率更高，这一特征由人类ABO和FUT2基因型共同决定，研究人员可以在坦桑尼亚队列中重现这种关联。
体外实验表明，GalNAc可作为携带GalNAc代谢途径的F. prausnitzii菌株的唯一碳水化合物来源。进一步的计算机和体外研究表明，其它与ABO相关的物种也可以利用GalNAc，特别是Collinsella aerofaciens。GalNAc利用基因也与宿主的心脏代谢健康有关，特别是在具有粘膜A抗原的个体中。
总之，这一研究结果表明，人类基因组和细菌宏基因组的基因关联可以为宿主-微生物组的相互关系提供功能性见解。
附：英文原文
Title: Host genetic regulation of human gut microbial structural variation
Author: Zhernakova, Daria V., Wang, Daoming, Liu, Lei, Andreu-Snchez, Sergio, Zhang, Yue, Ruiz-Moreno, Angel J., Peng, Haoran, Plomp, Niels, Del Castillo-Izquierdo, ngela, Gacesa, Ranko, Lopera-Maya, Esteban A., Temba, Godfrey S., Kullaya, Vesla I., van Leeuwen, Sander S., Xavier, Ramnik J., de Mast, Quirijn, Joosten, Leo A. B., Riksen, Niels P., Rutten, Joost H. W., Netea, Mihai G., Sanna, Serena, Wijmenga, Cisca, Weersma, Rinse K., Zhernakova, Alexandra, Harmsen, Hermie J. M., Fu, Jingyuan
Issue&Volume: 2024-01-03
Abstract: Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1,2,3,4,5,6, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host’s cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host–microbiome relationship.
DOI: 10.1038/s41586-023-06893-w
Source: https://www.nature.com/articles/s41586-023-06893-w
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
