Breast milk immune composition varies during the transition stage of lactation: characterization of immunotypes in the MAMI cohort

Karla Rio-Aige; Aina Fernández-Bargalló; Esteban Vegas-Lozano; Antonio Miñarro-Alonso; Margarida Castell; Marta Selma-Royo; Cecilia Martínez-Costa; Maria José Rodríguez-Lagunas; Maria Carmen Collado; Francisco José Pérez-Cano

doi:10.3389/fnut.2023.1252815

Breast milk immune composition varies during the transition stage of lactation: characterization of immunotypes in the MAMI cohort

Front Nutr. 2023 Nov 23:10:1252815. doi: 10.3389/fnut.2023.1252815. eCollection 2023.

Authors

Affiliations

¹ Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), Barcelona, Spain.
² Nutrition and Food Safety Research Institute (INSA-UB), Santa Coloma de Gramenet, Spain.
³ Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain.
⁴ CIBERFES, ISCIII, Madrid, Spain.
⁵ Institute of Agrochemistry and Food Technology (IATA-CSIC), National Research Council, Paterna, Spain.
⁶ Department of Pediatrics, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain.

Abstract

Background: Breast milk is a complex and dynamic fluid needed for infant development and protection due to its content of bioactive factors such as immunoglobulins (Igs). Most studies focus primarily on IgA, but other types of Ig and even other immune components (cytokines and adipokines) may also play significant roles in neonatal health. As a first step, we aimed to characterize the Ig profile, many cytokines, and two adipokines (leptin and adiponectin) at two sampling time points within the transitional stage, which is the least studied phase in terms of these components. The secondary objective was to identify different breast milk immunotypes in the MAMI cohort substudy, and finally, we further aimed at analyzing maternal and infant characteristics to identify influencing factors of breast milk immune composition.

Methods: Breast milk samples from 75 mothers were studied between days 7 and 15 postpartum. The Igs, cytokines, and adipokine levels were determined by a multiplex approach, except for the IgA, IgM, and leptin that were evaluated by ELISA.

Results: IgA, IgM, IgE, IgG2, IL-1β, IL-5, IL-6, IL-10, and IL-17 were significantly higher on day 7 with respect to day 15. The multiple factor analysis (MFA) allowed us to identify two maternal clusters (immunotypes) depending on the breast milk immune profile evolution from day 7 to day 15, mainly due to the IgE and IgG subtypes, but not for IgA and IgM, which always presented higher levels early in time.

Conclusion: All these results demonstrated the importance of the dynamics of the breast milk composition in terms of immune factors because even in the same lactation stage, a difference of 1 week has induced changes in the breast milk immune profile. Moreover, this immune profile does not evolve in the same way for all women. The dynamic compositional changes may be maternal-specific, as we observed differences in parity and exclusive breastfeeding between the two BM immunotype groups, which could potentially impact infant health.

Keywords: adipokines; breast milk; breastfeeding; cytokines; immunoglobulins; transitional stage.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by La Marató-TV3 (DIM-2-ELI, ref. 2018–27/30–31), the European Research Council under the European Union’s Horizon 2020 research and innovation program (ERC starting grant, no. 639 226), the MAMI project, and Plan Nacional RTI2018-097982-B-I00 (BABYBAC). KR-A holds a fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (FPU 19/05150). INSA acknowledges the excellence of the María de Maeztu program (CEX2021-001234-M) and IATA-CSIC the excellence of the Severo Ochoa program (CEX2021-001189-S/MCIN/AEI/10.13039/501100011033) both funded by MICIN/AEI/FEDER, UE.