Human breast milk regulates a baby's mix of microbes, or microbiome, during the infant's first year of life. This in turn lowers the child's risk of developing asthma, a new study shows.
Led by researchers at NYU Langone Health and the University of Manitoba, the study results showed that breastfeeding beyond three months supports the gradual maturation of the microbiome in the infant's digestive system and nasal cavity, the upper part of the respiratory tract. Conversely, stopping breastfeeding earlier than three months disrupts the paced development of the microbiome and was linked to a higher risk of preschool asthma.
Some components in breast milk, such as complex sugars called human milk oligosaccharides, can only be broken down with the help of certain microbes. This provides a competitive advantage to microbes capable of digesting these sugars. By contrast, infants who are weaned earlier than three months from breast milk and who then rely solely on formula feeding, become home to a different set of microbes — ones that will help the infant to digest the components in formula. While many of these microbes that thrive on formula do eventually end up in all babies, the researchers showed that their early arrival is linked to an increased risk of asthma.
"Just as a pacemaker regulates the rhythm of the heart, breastfeeding and human milk set the pace and sequence for microbial colonization in the infant's gut and nasal cavity, ensuring that this process occurs in an orderly and timely manner," said study co-senior investigator and computational biologist Liat Shenhav, PhD. "Healthy microbiome development is not only about having the right microbes. They also need to arrive in the right order at the right time," said Shenhav, an assistant professor at NYU Grossman School of Medicine, its Institute for Systems Genetics, and the School's Department of Microbiology.
For the study, Shenhav, who is also an assistant professor at NYU's Courant Institute of Mathematical Sciences, worked in collaboration with study co-senior investigator Meghan Azad, PhD, director of the Manitoba Interdisciplinary Lactation Center, and a professor of pediatrics and child health, at the University of Manitoba.
Another key study finding was that the bacterial species called Ruminococcus gnavus appeared much sooner in the guts of children who were weaned early from breast milk than in those of children who were exclusively breastfed. The bacterium is known to be involved in the production of molecules called short-chain fatty acids, and the formation and breakdown of the amino acid tryptophan. Both tryptophan and its metabolites have been linked to immune system regulation and disruption in previous research, including an increased risk of asthma. The study authors noted that beyond aiding in digestion, an infant's microbiome plays a crucial role in the immune system's development.
Publishing in the journal Cell online Sept. 19, the study tracked the ebb and flow of microbes in the guts and noses of infants during the first year of life, as well as details on breastfeeding and the composition of their mothers' milk. All the children and their mothers were participating in the CHILD Cohort Study, a long-term research project that has been studying the same 3,500 Canadian children at different stages of life from the womb well into adolescence.
The data provided by the CHILD Cohort Study enabled researchers to detangle the impact of breastfeeding on an infant's microbiome from a range of other environmental factors, including prenatal smoke exposure, antibiotics, and the mother's asthma history.
Even when these factors were accounted for, they found that breastfeeding duration remained a powerful determinant for the child's microbial makeup over time. They also used these microbial dynamics and data on milk components to train a machine-learning model that accurately predicted asthma years in advance. Finally, they created a statistical model to learn causal relationships, which showed that the primary way breastfeeding reduces asthma risk is through shaping the infant's microbiome.
"The algorithms we developed provide valuable insights into microbial dynamics during an infant's first year of life and how these microbes interacted with the infant," said Shenhav. "These insights allowed us to move beyond identifying associations, enhancing our ability to make predictions and explore causal relationships.
"Our research highlights the profound impact of breastfeeding on the infant microbiome and breastfeeding's essential role in supporting respiratory health. By uncovering the mechanisms behind the protective effects of breast milk, as demonstrated in this study, we aim to inform national guidelines on breastfeeding and weaning from breast milk in a data-driven manner.
"With further research, our findings could also contribute to developing strategies to prevent asthma in children who cannot be breastfed for at least three months," she added.
Funding support for the study was provided by National Institutes of Health grant DP2AI185753. Additional funding was provided by Genome British Columbia (274CHI), the University of British Columbia, CIHR CGS-D, the Canadian Institute for Advanced Research's Humans and the Microbiome program, and the Canada Research Chair Program. Study participants were all volunteers from families involved in the CHILD Cohort Study, which was initially funded by the Canadian Institute of Health Research (CIHR) and AllerGen NCE.
Besides Shenhav and Azad, other study co-senior investigators are Padmaja Subbarao at the University of Toronto and Michael Surrette at McMaster University in Hamilton.
Other study co-investigators include co-first author Kelsey Fehr and co-author Elinor Simons, both at the University of Manitoba; and co-authors Myrtha Reyna, Ruixue Dai, Theo Moraes, and Vanessa Breton at the University of Toronto; Charisse Petersen, Darlene Dai, and Stuart Turvey at the University of British Columbia; Laura Rossi and Marek Smieja at McMaster University; Michael A. Silverman and Maayan Levy at the University of Pennsylvania in Philadelphia; Lars Bode at the University of California, San Diego; Catherine Field and Piush Mandhane at the University of Alberta; and Jean S. Marshall from Dalhousie University in Halifax.
