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 Th2 to Th1 and Th17 dominant immune phenotypes 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.

Authors	Gao, Yuan; Nanan, Ralph; Macia, Laurence; Tan, Jian; Sominsky, Luba; Quinn, Thomas P; O'Hely, Martin; Ponsonby, Anne-Louise; Tang, Mimi Lk; Collier, Fiona; Strickland, Deborah H; Dhar, Poshmaal; Brix, Susanne; Phipps, Simon; Sly, Peter D; Ranganathan, Sarath; Stokholm, Jakob; Kristiansen, Karsten; Gray, Lawrence; Vuillermin, Peter
Journal	The Journal of allergy and clinical immunology
Pages	669-678
Volume	148
Date	1/01/2021
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.jaci.2021.07.011