Gut microbiota maturity mediates the protective effect of siblings on food allergy

Yuan Gao; Jakob Stokholm; Martin O'Hely; Anne-Louise Ponsonby; Mimi L K Tang; Sarath Ranganathan; Richard Saffery; Leonard C Harrison; Fiona Collier; Lawrence Gray; David Burgner; John Molloy; Peter D Sly; Susanne Brix; Hanne Frøkiær; Peter Vuillermin; BIS Investigator Group

doi:10.1016/j.jaci.2023.02.034

Gut microbiota maturity mediates the protective effect of siblings on food allergy

J Allergy Clin Immunol. 2023 Sep;152(3):667-675. doi: 10.1016/j.jaci.2023.02.034. Epub 2023 May 6.

Authors

Yuan Gao¹, Jakob Stokholm², Martin O'Hely³, Anne-Louise Ponsonby⁴, Mimi L K Tang⁵, Sarath Ranganathan⁵, Richard Saffery⁵, Leonard C Harrison⁶, Fiona Collier⁷, Lawrence Gray⁸, David Burgner⁵, John Molloy⁸, Peter D Sly⁹, Susanne Brix¹⁰, Hanne Frøkiær¹¹, Peter Vuillermin¹²; BIS Investigator Group

Affiliations

¹ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
³ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
⁴ Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia; Developing Brain Division, The Florey Institute for Neuroscience and Mental Health, Melbourne, Australia.
⁵ Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia; Department of Pediatrics, University of Melbourne, Melbourne, Australia.
⁶ Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
⁷ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia.
⁸ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia.
⁹ Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Australia; Faculty of Health, Deakin University, Geelong, Australia.
¹⁰ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
¹¹ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹² Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia. Electronic address: peter.vuillermin@deakin.edu.au.

PMID: 37150361
DOI: 10.1016/j.jaci.2023.02.034

Abstract

Background: The mechanisms underlying the protective effect of older siblings on allergic disease remain unclear but may relate to the infant gut microbiota.

Objective: We sought to investigate whether having older siblings decreases the risk of IgE-mediated food allergy by accelerating the maturation of the infant gut microbiota.

Methods: In a birth cohort assembled using an unselected antenatal sampling frame (n = 1074), fecal samples were collected at 1 month, 6 months, and 1 year, and food allergy status at 1 year was determined by skin prick test and in-hospital food challenge. We used 16S rRNA gene amplicon sequencing to derive amplicon sequence variants. Among a random subcohort (n = 323), microbiota-by-age z scores at each time point were calculated using fecal amplicon sequence variants to represent the gut microbiota maturation over the first year of life.

Results: A greater number of siblings was associated with a higher microbiota-by-age z score at age 1 year (β = 0.15 per an additional sibling; 95% CI, 0.05-0.24; P = .003), which was in turn associated with decreased odds of food allergy (odds ratio, 0.45; 95% CI, 0.33-0.61; P < .001). Microbiota-by-age z scores mediated 63% of the protective effect of siblings. Analogous associations were not observed at younger ages.

Conclusions: The protective effect of older siblings on the risk of developing IgE-mediated food allergy during infancy is substantially mediated by advanced maturation of the gut microbiota at age 1 year.

Keywords: Food allergy; birth cohort; microbiota maturation; siblings.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Food Hypersensitivity* / prevention & control
Gastrointestinal Microbiome*
Humans
Immunoglobulin E
Infant
Pregnancy
RNA, Ribosomal, 16S / genetics
Siblings

Substances

RNA, Ribosomal, 16S
Immunoglobulin E