Host genetic regulation of human gut microbial structural variation
Author:
Zhernakova Daria V.ORCID, Wang DaomingORCID, Liu LeiORCID, Andreu-Sánchez Sergio, Zhang Yue, Ruiz-Moreno Angel J.ORCID, Peng HaoranORCID, Plomp NielsORCID, Del Castillo-Izquierdo ÁngelaORCID, Gacesa RankoORCID, Lopera-Maya Esteban A., Temba Godfrey S., Kullaya Vesla I., van Leeuwen Sander S., Aguirre-Gamboa Raul, Deelen Patrick, Franke Lude, Kuivenhoven Jan A., Nolte Ilja M., Sanna Serena, Snieder Harold, Swertz Morris A., Visscher Peter M., Vonk Judith M., Xavier Ramnik J.ORCID, de Mast Quirijn, Joosten Leo A. B.ORCID, Riksen Niels P.ORCID, Rutten Joost H. W., Netea Mihai G.ORCID, Sanna Serena, Wijmenga CiscaORCID, Weersma Rinse K.ORCID, Zhernakova Alexandra, Harmsen Hermie J. M.ORCID, Fu JingyuanORCID,
Abstract
AbstractAlthough the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1–6, 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.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference89 articles.
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