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A mother's touch: microbial guardians of early immune imprinting

Melody Y Zeng1, Julia A Brown2

  • 1Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA.

Trends in Immunology
|October 8, 2025
PubMed

The evolution of the fetal immune system within the womb is a delicate balancing act: it is trained to not reject maternal antigens, while equipping itself with 'learned' immunity to survive and thrive in the outside world. In this opinion article, we propose that a deliberate maternal touch via immune and nutritional influences, orchestrated, in part, by microbiota-derived components, imprints the fetal immune system with the needed immune memory and epigenetic marks to navigate a far less nurturing outside world, including early microbial colonizers in the newborn's intestine, pathogens and irritants, and allergens in food. We redefine the hygiene hypothesis to include prenatal maternal microbial exposures, priming fetal immune development for long-term fitness and reduced inflammatory/autoimmune disease risk.

Keywords:
immune imprintingmaternal–fetal immune tolerancemetabolitemicrobiota

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