The maternal gut microbiome during pregnancy and offspring allergy and asthma

Yuan Gao; Ralph Nanan; Laurence Macia; Jian Tan; Luba Sominsky; Thomas P Quinn; Martin O'Hely; Anne-Louise Ponsonby; Mimi L K Tang; Fiona Collier; Deborah H Strickland; Poshmaal Dhar; Susanne Brix; Simon Phipps; Peter D Sly; Sarath Ranganathan; Jakob Stokholm; Karsten Kristiansen; Lawrence E K Gray; Peter Vuillermin

doi:10.1016/j.jaci.2021.07.011

The maternal gut microbiome during pregnancy and offspring allergy and asthma

J Allergy Clin Immunol. 2021 Sep;148(3):669-678. doi: 10.1016/j.jaci.2021.07.011. Epub 2021 Jul 24.

Authors

Yuan Gao¹, Ralph Nanan², Laurence Macia³, Jian Tan³, Luba Sominsky⁴, Thomas P Quinn⁵, Martin O'Hely⁶, Anne-Louise Ponsonby⁷, Mimi L K Tang⁸, Fiona Collier⁹, Deborah H Strickland¹⁰, Poshmaal Dhar⁹, Susanne Brix¹¹, Simon Phipps¹², Peter D Sly¹³, Sarath Ranganathan¹⁴, Jakob Stokholm¹⁵, Karsten Kristiansen¹⁶, Lawrence E K Gray¹⁷, Peter Vuillermin¹⁸

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 Charles Perkins Center, The University of Sydney, Sydney, Australia.
³ Charles Perkins Center, The University of Sydney, Sydney, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
⁴ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia.
⁵ Applied Artificial Intelligence Institute, Deakin University, Geelong, Australia.
⁶ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Murdoch Children's Research Institute, Melbourne, Australia.
⁷ Murdoch Children's Research Institute, Melbourne, Australia; Florey Institute, Melbourne, Australia; University of Melbourne, Melbourne, Australia; the Centre For Food Allergy Research, Murdoch Children's Research Institute, Parkville.
⁸ Murdoch Children's Research Institute, Melbourne, Australia; University of Melbourne, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia; the Centre For Food Allergy Research, Murdoch Children's Research Institute, Parkville.
⁹ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia.
¹⁰ Telethon Institute, Perth, Australia; University of Western Australia, Crawley, Australia.
¹¹ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
¹² QIMR Berghofer Medical Research Institute, Herston, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, Australia; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia.
¹³ Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Australia; Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, St Lucia, Australia.
¹⁴ Murdoch Children's Research Institute, Melbourne, Australia; University of Melbourne, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia.
¹⁵ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Slagelse Hospital, Slagelse, Denmark.
¹⁶ BGI-Shenzhen, Shenzhen, China; China National Genebank, Shenzhen, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia. Electronic address: Lawrence.gray@barwonhealth.org.au.
¹⁸ Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia; the Centre For Food Allergy Research, Murdoch Children's Research Institute, Parkville. Electronic address: peter.vuillermin@deakin.edu.au.

PMID: 34310928
DOI: 10.1016/j.jaci.2021.07.011

Abstract

Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant's risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow's milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and homeostasis following exposure to the extrauterine environment. Cellular and metabolic products of the maternal gut microbiome can promote the expression of microbial pattern recognition receptors, as well as thymic and bone marrow hematopoiesis relevant to regulatory immunity. At birth, transmission of maternally derived bacteria likely leverages this in utero programming to accelerate postnatal transition from a T_H2- to T_H1- and T_H17-dominant immune phenotype and maturation of regulatory immune mechanisms, which in turn reduce the child's risk of allergic disease and asthma. Although our understanding of these phenomena is rapidly evolving, the field is relatively nascent, and we are yet to translate existing knowledge into interventions that substantially reduce disease risk in humans. Here, we review evidence that the maternal gut microbiome impacts the offspring's risk of allergic disease and asthma, discuss challenges and future directions for the field, and propose the hypothesis that maternal carriage of Prevotella copri during pregnancy decreases the offspring's risk of allergic disease via production of succinate, which in turn promotes bone marrow myelopoiesis of dendritic cell precursors in the fetus.

Keywords: Gut microbiome; allergy; asthma; fetal immunity.

Publication types

Review

MeSH terms

Animals
Dietary Supplements
Female
Gastrointestinal Microbiome*
Humans
Hypersensitivity / epidemiology*
Infant, Newborn
Pregnancy
Probiotics
Risk