title: Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome.
abstract: Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system2to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Snijders
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Sasha A
authors.initials: SA
authors.lastname: Langley
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Young-Mo
authors.identifier: http://orcid.org/0000-0002-8972-7593
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Brislawn
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Noecker
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Erika M
authors.initials: EM
authors.lastname: Zink
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fansler
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Casey
authors.affiliation: Systems Genetics Core Facility, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Darla R
authors.initials: DR
authors.lastname: Miller
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.|Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Gary H
authors.identifier: http://orcid.org/0000-0003-1534-0385
authors.initials: GH
authors.lastname: Karpen
authors.affiliation: Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.affiliation: Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Brown
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98105, USA.|Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA.|Santa Fe Institute, Santa Fe, New Mexico 87501, USA.
authors.forename: Elhanan
authors.initials: E
authors.lastname: Borenstein
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
authors.affiliation: Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.affiliation: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
mesh_terms: D000818:Animals; D004032:Diet; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000382:microbiology*; D000071421:Life History Traits; D055442:Metabolome; D051379:Mice; D040641:Quantitative Trait Loci