New first-of-its-kind research from the CHILD Cohort Study (CHILD) provides insights into an important ingredient of human breastmilk: naturally occurring sugars known as human milk oligosaccharides, or HMOs. Published in Nature Communications, the research sheds light on the complex relationships among a mother’s genetic makeup, the HMOs in her breastmilk, and her baby’s respiratory health.
The study’s findings could inform new ways of predicting and preventing childhood disease, and could facilitate new HMO-based therapies to prevent respiratory illness.
The major, multi-year collaboration connected breastmilk researchers at the University of California San Diego and the University of Manitoba with bioinformatics and computational genomics experts at Queen’s University.
“Of course, we already know that breastfeeding provides many amazing health benefits,” comments co-author and CHILD Deputy Director Dr. Meghan Azad, a leading breastmilk researcher and University of Manitoba professor and Canada Research Chair in Early Nutrition and the Developmental Origins of Health and Disease.
“But we don’t fully understand how this works at the biological level,” added Dr. Azad, also a researcher with Children’s Hospital Research Institute of Manitoba. “Here we explored the complex dynamics among mothers, their milk and their babies to see how a mom’s genes influence the composition of HMOs in her milk, and how these HMOs interact with her baby’s genetics to influence their risk of later developing asthma.”
The researchers conducted genome-wide association studies (GWASs), which simultaneously looked at millions of DNA sequence variations and how they relate to varying concentrations of 19 different HMOs found in the milk of 980 mothers participating in CHILD. They then looked at whether exposure to these differences in HMOs were associated with risk of developing recurrent wheeze, an early symptom of asthma, among the breast-fed babies. A team led by Dr. Qingling Duan, a Queen’s National Scholar in Bioinformatics at Queen’s University, identified strongly correlated genetic variations among the moms and the HMO composition of their milk.
“My team was blown away by the significance of the GWAS signals between the maternal genomes and their HMO profiles,” notes Dr. Duan. “Moreover, while we had expected some associated loci, our study identified a number of novel genetic associations previously not known to be involved in HMO production.”
Even for genes previously known to influence HMO composition, the study revealed more about their potential biological functions and impact on more than one HMO.
“For example, from previous research, we knew that the FUT2 gene impacted the HMO profile of milk,” observes co-author Dr. Lars Bode of the University of California San Diego and Founding Director of the Human Milk Institute (HMI). “However, this new study shows us that FUT2 has a broader impact than expected: it doesn’t only affect HMOs with a chemical bond regulated by the FUT2 enzyme – it affects many others too, illustrating the remarkable ‘biosynthetic interconnectivity’ of HMOs.”
To test the strength of these findings, they conducted the same analysis in 395 mothers from another cohort, the INSPIRE Study, and found many of the same associations.
When it came to tracing the impact of HMOs on the babies’ later respiratory health, the researchers found that milk with different HMO profiles appeared to affect childhood respiratory outcomes—sometimes even overriding the risk carried in the children’s genes. Milk with high levels of specific HMOs tends to protect babies against later developing wheeze. This impact is particularly evident among children with high genetic risk of developing asthma.
By increasing our knowledge about how HMOs are produced and how they influence health, the study points to possible new advances in healthcare and medical research.
“The more we know about HMOs, how they are synthesized and what impact they have on human health, the better we can design helpful interventions to prevent childhood diseases,” says lead author Amirtha Ambalavanan, a postdoctoral research fellow in Biomedical & Molecular Sciences at Queen’s University.
“For example, these insights may allow us to develop HMO-inspired supplements for babies and to bioengineer specific HMOs for use in research—eventually perhaps even for use in therapies to treat respiratory diseases, in both children and adults.
“We have so much to learn from human milk.”
Read Dr. Azad’s “tweetorial” about this finding