Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization

Zhi Yi Fang; Sara A Stickley; Amirthagowri Ambalavanan; Yang Zhang; Amanda M Zacharias; Kelsey Fehr; Shirin Moossavi; Charisse Petersen; Kozeta Miliku; Piushkumar J Mandhane; Elinor Simons; Theo J Moraes; Malcolm R Sears; Michael G Surette; Padmaja Subbarao; Stuart E Turvey; Meghan B Azad; Qingling Duan

doi:10.1016/j.chom.2024.08.014

Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization

Cell Host Microbe. 2024 Oct 9;32(10):1838-1852.e5. doi: 10.1016/j.chom.2024.08.014. Epub 2024 Sep 17.

Authors

Zhi Yi Fang¹, Sara A Stickley¹, Amirthagowri Ambalavanan¹, Yang Zhang², Amanda M Zacharias¹, Kelsey Fehr³, Shirin Moossavi³, Charisse Petersen⁴, Kozeta Miliku⁵, Piushkumar J Mandhane⁶, Elinor Simons⁷, Theo J Moraes⁸, Malcolm R Sears⁹, Michael G Surette¹⁰, Padmaja Subbarao¹¹, Stuart E Turvey⁴, Meghan B Azad³, Qingling Duan¹²

Affiliations

¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
² School of Computing, Queen's University, Kingston, ON K7L 3N6, Canada.
³ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada.
⁴ Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
⁵ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Manitoba Interdisciplinary Lactation Centre (MILC), Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A1, Canada.
⁶ Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Section of Allergy and Immunology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁸ Department of Pediatrics, The Hospital for Sick Children, Toronto, ON M5G 1E8, Canada.
⁹ Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
¹⁰ Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
¹¹ Department of Pediatrics, The Hospital for Sick Children, Toronto, ON M5G 1E8, Canada; Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada.
¹² Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada; School of Computing, Queen's University, Kingston, ON K7L 3N6, Canada. Electronic address: [email protected].

PMID: 39293435
DOI: 10.1016/j.chom.2024.08.014

Abstract

The human milk microbiota (HMM) is thought to influence the long-term health of offspring. However, its role in asthma and atopy and the impact of host genomics on HMM composition remain unclear. Through the CHILD Cohort Study, we followed 885 pregnant mothers and their offspring from birth to 5 years and determined that HMM was associated with maternal genomics and prevalence of childhood asthma and allergic sensitization (atopy) among human milk-fed infants. Network analysis identified modules of correlated microbes in human milk that were associated with subsequent asthma and atopy in preschool-aged children. Moreover, reduced alpha-diversity and increased Lawsonella abundance in HMM were associated with increased prevalence of childhood atopy. Genome-wide association studies (GWASs) identified maternal genetic loci (e.g., ADAMTS8, NPR1, and COTL1) associated with HMM implicated with asthma and atopy, notably Lawsonella and alpha-diversity. Thus, our study elucidates the role of host genomics on the HMM and its potential impact on childhood asthma and atopy.

Keywords: GWASs; HMM; allergic sensitization; asthma; atopy; early-life exposures; genome-wide association studies; human milk microbiota; network analysis; prospective cohort study.

MeSH terms

Adult
Asthma* / genetics
Asthma* / immunology
Asthma* / microbiology
Child, Preschool
Cohort Studies
Female
Genome-Wide Association Study*
Genomics
Humans
Hypersensitivity* / genetics
Hypersensitivity* / microbiology
Infant
Infant, Newborn
Male
Microbiota*
Milk, Human* / immunology
Milk, Human* / microbiology
Pregnancy