Author
Listed:
- Daria V. Zhernakova
(University of Groningen, University Medical Center Groningen, Department of Genetics)
- Daoming Wang
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Pediatrics)
- Lei Liu
(University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention)
- Sergio Andreu-Sánchez
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Pediatrics)
- Yue Zhang
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Pediatrics)
- Angel J. Ruiz-Moreno
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Pediatrics)
- Haoran Peng
(University of Groningen, University Medical Center Groningen, Department of Genetics)
- Niels Plomp
(University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology)
- Ángela Castillo-Izquierdo
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention)
- Ranko Gacesa
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology)
- Esteban A. Lopera-Maya
(University of Groningen, University Medical Center Groningen, Department of Genetics)
- Godfrey S. Temba
(Radboud University Medical Center
Kilimanjaro Christian Medical University College
Radboud University Medical Center)
- Vesla I. Kullaya
(Kilimanjaro Christian Medical University College
Kilimanjaro Christian Medical Center)
- Sander S. van Leeuwen
(University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine)
- Ramnik J. Xavier
(Broad Institute of MIT and Harvard
Massachusetts General Hospital)
- Quirijn de Mast
(Radboud University Medical Center
Radboud University Medical Center)
- Leo A. B. Joosten
(Radboud University Medical Center
Iuliu Haţieganu University of Medicine and Pharmacy)
- Niels P. Riksen
(Radboud University Medical Center)
- Joost H. W. Rutten
(Radboud University Medical Center)
- Mihai G. Netea
(Radboud University Medical Center
Radboud University Medical Center
University of Bonn
Craiova University of Medicine and Pharmacy)
- Serena Sanna
(University of Groningen, University Medical Center Groningen, Department of Genetics
National Research Council)
- Cisca Wijmenga
(University of Groningen, University Medical Center Groningen, Department of Genetics)
- Rinse K. Weersma
(University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology)
- Alexandra Zhernakova
(University of Groningen, University Medical Center Groningen, Department of Genetics)
- Hermie J. M. Harmsen
(University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention)
- Jingyuan Fu
(University of Groningen, University Medical Center Groningen, Department of Genetics
University of Groningen, University Medical Center Groningen, Department of Pediatrics)
Abstract
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 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.
Suggested Citation
Daria V. Zhernakova & Daoming Wang & Lei Liu & Sergio Andreu-Sánchez & Yue Zhang & Angel J. Ruiz-Moreno & Haoran Peng & Niels Plomp & Ángela Castillo-Izquierdo & Ranko Gacesa & Esteban A. Lopera-Maya , 2024.
"Host genetic regulation of human gut microbial structural variation,"
Nature, Nature, vol. 625(7996), pages 813-821, January.
Handle:
RePEc:nat:nature:v:625:y:2024:i:7996:d:10.1038_s41586-023-06893-w
DOI: 10.1038/s41586-023-06893-w
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