Breastfeeding enrichment of B. longum subsp. infantis mitigates the effect of antibiotics on the microbiota and childhood asthma risk

Darlene L Y Dai, Charisse Petersen, Courtney Hoskinson, Kate L Del Bel, Allan B Becker, Theo J Moraes, Piushkumar J Mandhane, B Brett Finlay, Elinor Simons, Anita L Kozyrskyj, David M Patrick, Padmaja Subbarao, Lars Bode, Meghan B Azad, Stuart E Turvey, Darlene L Y Dai, Charisse Petersen, Courtney Hoskinson, Kate L Del Bel, Allan B Becker, Theo J Moraes, Piushkumar J Mandhane, B Brett Finlay, Elinor Simons, Anita L Kozyrskyj, David M Patrick, Padmaja Subbarao, Lars Bode, Meghan B Azad, Stuart E Turvey

Abstract

Background: Early antibiotic exposure is linked to persistent disruption of the infant gut microbiome and subsequent elevated pediatric asthma risk. Breastfeeding acts as a primary modulator of the gut microbiome during early life, but its effect on asthma development has remained unclear.

Methods: We harnessed the CHILD cohort to interrogate the influence of breastfeeding on antibiotic-associated asthma risk in a subset of children (n = 2,521). We then profiled the infant microbiomes in a subset of these children (n = 1,338) using shotgun metagenomic sequencing and compared human milk oligosaccharide and fatty acid composition from paired maternal human milk samples for 561 of these infants.

Findings: Children who took antibiotics without breastfeeding had 3-fold higher asthma odds, whereas there was no such association in children who received antibiotics while breastfeeding. This benefit was associated with widespread "re-balancing" of taxonomic and functional components of the infant microbiome. Functional changes associated with asthma protection were linked to enriched Bifidobacterium longum subsp. infantis colonization. Network analysis identified a selection of fucosylated human milk oligosaccharides in paired maternal samples that were positively associated with B. infantis and these broader functional changes.

Conclusions: Our data suggest that breastfeeding and antibiotics have opposing effects on the infant microbiome and that breastfeeding enrichment of B. infantis is associated with reduced antibiotic-associated asthma risk.

Funding: This work was supported in part by the Canadian Institutes of Health Research; the Allergy, Genes and Environment Network of Centres of Excellence; Genome Canada; and Genome British Columbia.

Keywords: HMOs; Translation to population health; antibiotics; asthma; breastfeeding; fatty acid; human milk; microbiome.

Conflict of interest statement

Declaration of interests M.B.A. receives research funding from the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Bill and Melinda Gates Foundation, the Manitoba Children’s Hospital Foundation, Prolacta Biosciences, Mitacs, CIFAR, the Garfield Weston Foundation, Health Data Research UK, and the Canadian COVID Immunity Task Force. She has consulted for DSM Nutritional Products and serves on the Malaika Vx and Tiny Health Scientific Advisory Boards.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Source: PubMed

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