Microbial colonization programs are structured by breastfeeding and guide healthy respiratory development

Liat Shenhav; Kelsey Fehr; Myrtha E Reyna; Charisse Petersen; Darlene L Y Dai; Ruixue Dai; Vanessa Breton; Laura Rossi; Marek Smieja; Elinor Simons; Michael A Silverman; Maayan Levy; Lars Bode; Catherine J Field; Jean S Marshall; Theo J Moraes; Piush J Mandhane; Stuart E Turvey; Padmaja Subbarao; Michael G Surette; Meghan B Azad

doi:10.1016/j.cell.2024.07.022

Microbial colonization programs are structured by breastfeeding and guide healthy respiratory development

Cell. 2024 Sep 19;187(19):5431-5452.e20. doi: 10.1016/j.cell.2024.07.022.

Authors

Liat Shenhav¹, Kelsey Fehr², Myrtha E Reyna³, Charisse Petersen⁴, Darlene L Y Dai⁴, Ruixue Dai³, Vanessa Breton³, Laura Rossi⁵, Marek Smieja⁵, Elinor Simons², Michael A Silverman⁶, Maayan Levy⁷, Lars Bode⁸, Catherine J Field⁹, Jean S Marshall¹⁰, Theo J Moraes³, Piush J Mandhane¹¹, Stuart E Turvey⁴, Padmaja Subbarao¹², Michael G Surette¹³, Meghan B Azad¹⁴

Affiliations

¹ Institute for Systems Genetics, New York Grossman School of Medicine, New York University, New York, NY, USA; Department of Microbiology, New York Grossman School of Medicine, New York University, New York, NY, USA; Department of Computer Science, Courant Institute of Mathematical Sciences, New York University, New York, NY, USA. Electronic address: liat.shenhav@nyulangone.org.
² Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada; Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
³ Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Division of Infectious Disease, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), University of California, San Diego, La Jolla, CA, USA; Human Milk Institute (HMI), University of California, San Diego, La Jolla, CA, USA.
⁹ Department of Agriculture, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
¹⁰ Department of Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada.
¹¹ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
¹² Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada. Electronic address: padmaja.subbarao@sickkids.ca.
¹³ Department of Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: surette@mcmaster.ca.
¹⁴ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada; Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. Electronic address: meghan.azad@umanitoba.ca.

PMID: 39303691
PMCID: PMC11531244 (available on 2025-09-19)
DOI: 10.1016/j.cell.2024.07.022

Abstract

Breastfeeding and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal milk composition of 2,227 children from the CHILD Cohort Study. We identified robust colonization patterns that, together with milk components, predict preschool asthma and mediate the protective effects of breastfeeding. We found that early cessation of breastfeeding (before 3 months) leads to the premature acquisition of microbial species and functions, including Ruminococcus gnavus and tryptophan biosynthesis, which were previously linked to immune modulation and asthma. Conversely, longer exclusive breastfeeding supports a paced microbial development, protecting against asthma. These findings underscore the importance of extended breastfeeding for respiratory health and highlight potential microbial targets for intervention.

Keywords: asthma; breastfeeding; computational biology; development; early life; gut microbiome; human milk; machine learning; microbial dynamics; microbiome development; nasal microbiome; respiratory health.

MeSH terms

Asthma / immunology
Asthma / microbiology
Asthma / prevention & control
Breast Feeding*
Child, Preschool
Cohort Studies
Female
Gastrointestinal Microbiome
Humans
Infant
Infant, Newborn
Male
Microbiota
Milk, Human* / microbiology

Grants and funding

DP2 AI185753/AI/NIAID NIH HHS/United States