title: Population-level analysis of gut microbiome variation.
abstract: Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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, 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: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Youssef
authors.initials: Y
authors.lastname: Darzi
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Karoline
authors.initials: K
authors.lastname: Faust
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, 9700 RB Groningen, Netherlands.
authors.forename: Marc Jan
authors.initials: MJ
authors.lastname: Bonder
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Mireia
authors.initials: M
authors.lastname: Valles-Colomer
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Doris
authors.initials: D
authors.lastname: Vandeputte
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Raul Y
authors.initials: RY
authors.lastname: Tito
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Samuel
authors.initials: S
authors.lastname: Chaffron
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Leen
authors.initials: L
authors.lastname: Rymenans
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Chloë
authors.initials: C
authors.lastname: Verspecht
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Lise
authors.initials: L
authors.lastname: De Sutter
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Gipsi
authors.initials: G
authors.lastname: Lima-Mendez
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, 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: Kevin
authors.initials: K
authors.lastname: D'hoe
authors.affiliation: VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Jonckheere
authors.affiliation: VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Homola
authors.affiliation: VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Roberto
authors.initials: R
authors.lastname: Garcia
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands.
authors.forename: Ettje F
authors.initials: EF
authors.lastname: Tigchelaar
authors.affiliation: VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium.
authors.forename: Linda
authors.initials: L
authors.lastname: Eeckhaudt
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. University of Groningen, University Medical Center Groningen, Department of Pediatrics, 9700 RB Groningen, Netherlands.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fu
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. KU Leuven-University Hospitals Leuven, Department of General Internal Medicine, Leuven, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Henckaerts
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands. Top Institute Food and Nutrition, Wageningen, Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. VIB, Center for the Biology of Disease, Leuven, Belgium. Vrije Universiteit Brussel, Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Brussels, Belgium. jeroen.raes@kuleuven.be.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
mesh_terms: D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D001530:Belgium; D015331:Cohort Studies; D004347:Drug Interactions; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans