title: Shifts in Lachnospira and Clostridium sp. in the 3-month stool microbiome are associated with preschool age asthma.
abstract: Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval)= 1.8-124.7; quartile 2: OR=1.0, ns; quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development.
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada, V6T 1Z3.|Child & Family Research Institute and BC Children's Hospital, Vancouver, Canada, V5Z 4H4.
authors.forename: Leah T
authors.initials: LT
authors.lastname: Stiemsma
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada, V6T 1Z3.|Michael Smith Laboratories, University of British Columbia, Vancouver, Canada, V6T 1Z4.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Arrieta
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Dimitriu
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, Canada, V5Z 4H4.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, Canada, V6T 1Z4.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thorson
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada, L8S 4K1.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Lefebvre
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada, R3A 1S1.
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Azad
authors.affiliation: Department of Pediatrics, University of Toronto, Toronto, Canada, M5S 1A1.|Hospital for Sick Children, Toronto, Canada, M5G 1X8.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Subbarao
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada, T6G 1C9.|School of Public Health, University of Alberta, Edmonton, Canada, T6G 1C9.
authors.forename: Piush
authors.initials: P
authors.lastname: Mandhane
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada, R3A 1S1.
authors.forename: Allan
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada, L8S 4K1.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Sears
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, Canada, V5Z 4H4.|Department of Pediatrics, University of British Columbia, Vancouver, Canada, V6H 3V4.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.affiliation: Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada, V6T 1Z3 sturvey@cfri.ca bfinlay@mail.ubc.ca.|Michael Smith Laboratories, University of British Columbia, Vancouver, Canada, V6T 1Z4.|Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada, V6T 1Z3.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.affiliation: Child & Family Research Institute and BC Children's Hospital, Vancouver, Canada, V5Z 4H4 sturvey@cfri.ca bfinlay@mail.ubc.ca.|Department of Pediatrics, University of British Columbia, Vancouver, Canada, V6H 3V4.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
mesh_terms: D001249:Asthma / Q000382:microbiology*; D002170:Canada; D016022:Case-Control Studies; D002675:Child, Preschool; D003013:Clostridium / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000068536:Bacillota / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007223:Infant; D008297:Male
keywords: atopic disease; dysbiosis; gut microbiota; hygiene hypothesis; microflora hypothesis