title: Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity.
abstract: Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurilshikov
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
authors.forename: Marc Jan
authors.initials: MJ
authors.lastname: Bonder
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands.
authors.forename: Ettje F
authors.initials: EF
authors.lastname: Tigchelaar
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schirmer
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Computer Science, Aalto University School of Science, Espoo, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Vatanen
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Zlatan
authors.initials: Z
authors.lastname: Mujagic
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands.
authors.forename: Arnau Vich
authors.initials: AV
authors.lastname: Vila
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Gwen
authors.initials: G
authors.lastname: Falony
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Vieira-Silva
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Imhann
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands.
authors.forename: Eelke
authors.initials: E
authors.lastname: Brandsma
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
authors.forename: Soesma A
authors.initials: SA
authors.lastname: Jankipersadsing
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Joossens
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. Microbial Ecology, Nutrition and Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain. Department of Pediatrics, Dr. Peset University Hospital, Valencia, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Cenit
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Deelen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, Netherlands.
authors.forename: Morris A
authors.initials: MA
authors.lastname: Swertz
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands.
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands. Division of Human Nutrition, Wageningen University, Wageningen, Netherlands.
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Gevers
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Daisy
authors.initials: D
authors.lastname: Jonkers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Novosibirsk State University, Novosibirsk, Russia. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. PolyOmica, Groningen, Netherlands. Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands.
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands. a.zhernakova@umcg.nl c.wijmenga@umcg.nl j.fu@umcg.nl.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fu
mesh_terms: D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D053379:Chromogranin A / Q000032:analysis / Q000378:metabolism; D004032:Diet; D019858:Enteroendocrine Cells / Q000378:metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005819:Genetic Markers; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056186:Metagenomics; D009426:Netherlands; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D053379:Chromogranin A; D005819:Genetic Markers; D012336:RNA, Ribosomal, 16S