Allergy. 2025 Nov 27. doi: 10.1111/all.70167. Online ahead of print.
ABSTRACT
BACKGROUND: Early-life microbial exposure to microbes may play a role in asthma development. This study tests the hypothesis that mothers born in low-income countries might have been exposed to diverse microbes-leading to greater diversity and higher levels of transplacental anti-microbial antibodies, thereby conferring protection against asthma in offspring.
METHODS: In the prospective Boston Birth Cohort, IgG antibody reactome against microbes (2740 species; 1311 genera) was profiled in cord blood, using Phage ImmunoPrecipitation Sequencing. Multinomial regression models were applied to examine the associations of cord blood IgG reactome with child risk of physician-diagnosed atopy and asthma. Mediation analysis was performed to examine the inter-relationships among maternal nativity, IgG reactome and risk of developing childhood asthma.
RESULTS: This report included 943 mother-child dyads enrolled at birth and followed prospectively. Compared to children of US-born mothers, children of foreign-born mothers had a lower prevalence of asthma (17.5% vs. 30.5%) and greater diversity of cord blood IgG antibodies against hundreds of microbes (FDR < 0.05). Cord blood seropositivity to peptides or proteins from 6 microbes was inversely associated with the risk of asthma in children, and children with more seropositivity to these microbes were at a lower risk of developing asthma (p < 0.001). IgG seropositivity to A. actinomycetemcomitans, H. pylori, S. flexneri, and T. parva each mediated 17%-62% of the association between maternal nativity and child risk of asthma.
CONCLUSION: In this US prospective birth cohort, maternal transplacental IgG reactivity to four microbes (A. actinomycetemcomitans, H. pylori, S. flexneri and T. parva) was associated with a lower risk of childhood asthma, and partly explains the lower risk of asthma in children of mothers born outside the US.
PMID:41307260 | DOI:10.1111/all.70167
