title: Early infancy microbial and metabolic alterations affect risk of childhood asthma.
abstract: Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Arrieta
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Child & Family Research Institute and BC Children's Hospital, Vancouver, British Columbia V4Z 4H4, Canada.
authors.forename: Leah T
authors.initials: LT
authors.lastname: Stiemsma
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Dimitriu
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thorson
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Russell
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Yurist-Doutsch
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, British Columbia V4Z 4H4, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Kuzeljevic
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Britton
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Lefebvre
authors.affiliation: Department of Pediatrics, University of Toronto, Toronto, Ontario M5S 2J7, Canada. Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Subbarao
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2R3, Canada. School of Public Health, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
authors.forename: Piush
authors.initials: P
authors.lastname: Mandhane
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Becker
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Sears
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, British Columbia V4Z 4H4, Canada. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kollmann
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, British Columbia V4Z 4H4, Canada. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. sturvey@cw.bc.ca bfinlay@mail.ubc.ca.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. sturvey@cw.bc.ca bfinlay@mail.ubc.ca.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D001249:Asthma / Q000382:microbiology*; D002648:Child; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007223:Infant; D055442:Metabolome; D051379:Mice; D064307:Microbiota; D010641:Phenotype; D011014:Pneumonia / Q000382:microbiology; D012307:Risk Factors; D012984:Software