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Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting - 04/08/18

Doi : 10.1016/j.jaci.2017.08.041 
Marie-Claire Arrieta, PhD a, b, c, Andrea Arévalo, MSc d, Leah Stiemsma, PhD e, f, Pedro Dimitriu, PhD g, Martha E. Chico, MD h, Sofia Loor, BSc h, Maritza Vaca, MD h, Rozlyn C.T. Boutin, BSc a, Evan Morien, MSc i, Mingliang Jin, PhD j, Stuart E. Turvey, MBBS, DPhil e, Jens Walter, PhD j, Laura Wegener Parfrey, PhD i, Philip J. Cooper, PhD d, h, k, , Brett Finlay, PhD a, g, l,
a Michael Smith Laboratories and the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada 
g Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada 
i Departments of Zoology and Botany, University of British Columbia, Vancouver, British Columbia, Canada 
l Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada 
b Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada 
c Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada 
d Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador 
e Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada 
f Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, Calif 
h Fundación Ecuatoriana Para Investigación en Salud, Quito, Ecuador 
j Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada 
k Institute of Infection and Immunity, St George's University of London, London, United Kingdom 

Corresponding author: Brett Finlay, PhD, Michael Smith Laboratories, #301-2185 East Mall, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.Michael Smith Laboratories#301-2185 East MallUniversity of British ColumbiaVancouverBritish ColumbiaV6T 1Z4Canada

Abstract

Background

Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.

Objective

We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.

Methods

We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.

Results

As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.

Conclusions

Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

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Graphical abstract




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Key words : Asthma, atopy, wheeze, gut microbiome, mycobiome, short-chain fatty acids, nonindustrialized setting

Abbreviations used : AW, CHILD, MaAsLin, MED, OTU, PICRUSt, qPCR, SCFA


Plan


 Supported by the Canadian Institutes of Health Research (CIHR) and Allergen grants to BFF and the ECUAVIDA cohort by the Wellcome Trust (grant 088862/Z/09/Z). L.T.S. is supported on a T32 Training Grant from the National Institutes of Health (5T32CA009142-37).
 Disclosure of potential conflict of interest: M.-C. Arrieta has received a grant from Allergen Canada and the Canadian Institute for Health Research and is employed by the University of Calgary. L. Stiemsma has received grants from the UBC Four Year Fellowship and the National Institutes of Health (T32CA009142), is employed by the University of California Los Angeles, has received royalties from PCT/CA2016/000065 “Bacterial Compositions and Methods of Use Thereof,” and has received travel support from AllerGen Networks Centres of Excellence Travel Award. E. Morien has received a grant from Human Frontiers in Science program (RGY0078/2015). M. Jin is employed as a visiting professor at the University of Alberta. L. W. Parfrey has received a grant from the Human Frontiers in Science program (RGY0078/2015) and has received travel support from the Canadian Institute for Advanced Research, Dalhousie University, and the Human Frontiers in Science Program. P. Cooper has received a grant from the Wellcome Trust and is employed by St George's University of London. B. Finlay has received grants from Allergen, the Canadian Institute for Health Research, and the Gates Foundation; has a board membership with Microbiome Insights; has consultant arrangements with Commense and Vedanta; and is employed by the University of British Columbia. The rest of the authors declare that they have no relevant conflicts of interest.


© 2017  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 142 - N° 2

P. 424 - août 2018 Retour au numéro
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