Breastfeeding promotes early neonatal regulatory T-cell expansion and immune tolerance of non-inherited maternal antigens

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Background: Breastfeeding is associated with long‐term health benefits, such as a lower incidence of childhood infections, asthma, obesity and autoimmune disorders. However, little is known regarding how the maternal and neonatal immune systems interact after parturition when the neonate receives nutrition from maternal breast milk.

Methods: We undertook a comparative analysis of immune repertoire and function at birth and 3 weeks of age in a cohort of 38 term neonates born by caesarean section grouped according to feeding method (breast milk versus formula). We used flow cytometry to study the immune phenotype in neonatal and maternal blood samples and mixed lymphocyte reactions to establish the proliferation response of neonatal versus maternal lymphocytes and vice versa. The microbiome of neonatal stool samples was also investigated using 16S rRNA sequencing.

Results: We show that the proportion of regulatory T cells (Tregs) increases in this period and is nearly twofold higher in exclusively breastfed neonates compared with those who received formula milk only. Moreover, breastfed neonates show a specific and Treg‐dependent reduction in proliferative T‐cell responses to non‐inherited maternal antigens (NIMA), associated with a reduction in inflammatory cytokine production. We also observed the enrichment of short chain fatty acid producing taxa (Veillonella and Gemella) in stool samples of exclusively breastfed neonates.

Conclusions: These data indicate that exposure of the neonate to maternal cells through breastfeeding acts to drive the maturation of Tregs and ‘tolerizes’ the neonate towards NIMA.

Bibliographic note

Funding Information: We are grateful for the guidance of our late colleague, mentor and friend, Shree Vishna Rasiah, and dedicate this work to his memory. We wish to thank Diane Mellers for coordinating the enrolment of study participants and the research midwives at Birmingham Women’s Hospital for their support. We are also grateful for the technical support of Sam Nicol and Kriti Verma. A.A. was supported by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC), Birmingham, UK. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service or the National Institute for Health Research. Publisher Copyright: © 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.


Original languageEnglish
Early online date12 Jan 2021
Publication statusE-pub ahead of print - 12 Jan 2021


  • Th17, breastfeeding, microbiome, neonate, non-inherited maternal antigen, regulatory T cell

ASJC Scopus subject areas

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