Plasma metabolomic signature of breastfeeding and risk of cardiometabolic diseases
Breastfeeding is inversely associated with cardiometabolic disease incidence in prospective studies; however, the metabolic pathways underlying these associations remain largely unknown. Here, we derive a plasma metabolomic score of lifetime total duration of breastfeeding using elastic net regularized regression in Nurses' Health Studies (n = 4349) and replicate in the Women's Health Initiative (n = 2088). Data include 181 untargeted plasma metabolites profiled by liquid chromatography mass spectrometry using blood samples collected in mid-life, and self-reported lifetime total duration of breastfeeding. We then examine the associations between the metabolite-based breastfeeding score and risk of T2D and CVD using multivariable Cox regression models and replicated in two external cohorts. The metabolite-based breastfeeding score comprised of 5 metabolites (i.e., C54:2 triglyceride, C56:2 triglyceride, C56:3 triglyceride, cotinine, indole-3-propionate), which show a modest but statistically significant correlation with lifetime total duration of breastfeeding. The metabolite-based breastfeeding score significantly inversely associate with T2D incidence (HR = 0.76, 95%CI = 0.71-0.82) and with CVD incidence (HR = 0.88, 95%CI = 0.84-0.93) independent of T2D and CVD risk factors. We identify plasma metabolite profiles in mid-life associated with breastfeeding duration, which is also linked to CVD and T2D risk.
Authors
- Anne‐Julie Tessier (ORCID: https://orcid.org/0000-0003-4551-1640)
- Raji Balasubramanian (ORCID: https://orcid.org/0000-0002-1488-1692)
- Aladdin H. Shadyab (ORCID: https://orcid.org/0000-0002-9693-0522)
- Rachel Sinkey (ORCID: https://orcid.org/0000-0001-7674-9796)
- Cristina Razquín (ORCID: https://orcid.org/0000-0003-3480-2645)
- Bernhard Haring (ORCID: https://orcid.org/0000-0001-6109-431X)
- Sylvia H. Ley (ORCID: https://orcid.org/0000-0003-0084-2630)
- Marta Guasch‐Ferré
- JoAnn E. Manson (ORCID: https://orcid.org/0000-0002-9426-7595)
- Kathryn M. Rexrode (ORCID: https://orcid.org/0000-0003-3387-8429)
- Zhila Semnani‐Azad (ORCID: https://orcid.org/0000-0001-7822-5072)
- Frank B. Hu (ORCID: https://orcid.org/0000-0002-8233-6274)
- Miguel Ángel Martínez‐González (ORCID: https://orcid.org/0000-0002-3917-9808)
- Oana A. Zeleznik (ORCID: https://orcid.org/0000-0002-8705-1163)
- Cuilin Zhang (ORCID: https://orcid.org/0000-0002-8014-2708)
- Anna Birukov (ORCID: https://orcid.org/0000-0002-8306-3351)
- Naoko Sasamoto (ORCID: https://orcid.org/0000-0002-4526-2181)
- Jennifer M. Mongiovi (ORCID: https://orcid.org/0000-0002-2083-8359)
- Lin Nan (ORCID: https://orcid.org/0000-0001-7731-0072)
- Fenglei Wang (ORCID: https://orcid.org/0000-0002-3850-2482)
Institutions
- Tulane University (US)
- University of Copenhagen (DK)
- Brigham and Women's Hospital (US)
- Albert Einstein College of Medicine (US)
- Harvard University (US)
- National University of Singapore (SG)
- University of Toronto (CA)
- University of Washington (US)
- University of Massachusetts Amherst (US)
- Montreal Heart Institute (CA)
- Novo Nordisk Foundation (DK)
- Instituto de Salud Carlos III (ES)
- University of Alabama at Birmingham (US)
- University of California San Diego (US)
- Fred Hutch Cancer Center (US)
- Human Longevity (United States) (US)
- German Institute of Human Nutrition (DE)
- Université de Montréal (CA)
- Saarland University (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-08
- DOI
- https://doi.org/10.1038/s41467-025-65977-5
- Primary Topic
- Breastfeeding Practices and Influences
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- Brigham and Women's Hospital
- Deutsche Forschungsgemeinschaft
- Novo Nordisk
- Novo Nordisk Fonden
- National Institutes of Health
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute