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Host genetic regulation of human gut microbial structural variation

Although 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 microbes. Here we conducted a meta-analysis of 
associations between human genetic variation and gut microbial structural variations 
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

Year of publication





Zeevi, D.
Korem, T.
Godneva, A.
Bar, N.
Kurilshikov, A.
Lotan-Pompan, M.
et al.

Full publication

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