BBreast milk not only provides nutrition, but also provides immune elements to your baby and regulates the microbiota. However, although researchers know that breast milk is a highly complex fluid containing hundreds of bioactive molecules, they do not know much about what determines and modulates the composition of breast milk. Kelsey JohnsonA geneticist at the University of Minnesota, she studies how external factors affect breast milk. Recent ResearchPublication year Nature CommunicationsShe used a multi-omics approach to characterize breast milk composition and found that maternal cytomegalovirus (CMV) infection can affect breast milk composition and alter the composition of the infant’s gut microbiota, thereby impeding growth during the first month of life.1
Kelsey Johnson has developed methods to characterize the hundreds of bioactive factors in breast milk and investigate what influences them.
University of Minnesota
Human CMV infection is highly prevalent and the virus About 85 percent of the world’s population.2 During lactation, CMV reactivates locally in the mammary gland, so it can also be transmitted from mother to infant in utero, but CMV is commonly transmitted through breast milk.1 Johnson noted that transmission of CMV through breast milk is an emerging concern. Causes serious complications Preterm infants are at risk for sepsis, thrombocytopenia, and long-term neurodevelopmental disorders.3
Johnson used his background in genomics to seek a broader understanding of the impact of CMV activation on breast milk composition. “To date, most studies on breast milk have looked at one or a few components of interest based on specific maternal characteristics,” Johnson explains. Instead of this approach, Johnson and his colleagues decided to use omics technologies to examine CMV-associated transcriptomic and metabolomic changes in breast milk.
The researchers first sequenced breast milk samples from lactating mothers one month after delivery, looking for CMV DNA to confirm the presence of the virus in the samples. They then performed transcriptomic analysis of these samples and found that 34 genes were upregulated in CMV-positive breast milk compared to CMV-negative breast milk. Many of these genes were associated with immune response-related pathways. Johnson further used publicly available single-cell RNA sequencing data to find that these 34 upregulated genes tended to be more highly expressed in immune cells. Perhaps unsurprisingly, CMV-positive breast milk samples had a higher estimated percentage of immune cells compared to CMV-negative breast milk.
In the transcriptome analysis, IDO1the gene encoding indoleamine 2,3-dioxygenase (IDO) was upregulated. IDO is the rate-limiting enzyme in the metabolic pathway from tryptophan to kynurenine. Thus, metabolomic analysis investigating 458 metabolites revealed two molecules that were increased in CMV-positive breast milk samples: kynurenine and its metabolite kynurenic acid.
Johnson said the presence of CMV in breast milk: IDO1 “The tryptophan-to-kynurenine metabolic pathway is likely important because the immune response to CMV in human cells and primordial tissues also activates this pathway. But she is fascinated by this pathway because of its potential to regulate the infant gut.”Bifidobacteria “Tryptophan availability in the infant gut may have a positive impact on the development of the microbiome and the infant’s immune status. Although we were not able to explore those pathways in this study, it is intriguing that these differences exist.”
This study is a very good example of where the field is heading and can help us determine what questions to ask next.
—Britt Goods, Dartmouth College
Finally, Johnson and her colleagues obtained fecal metagenomic data from full-term infants to investigate potential changes in the gut microbiome resulting from breast milk containing CMV. They found that infants exposed to CMV-positive breast milk: Bifidobacteria Species and population growth Clostridium tertiumOther researchers have demonstrated both of these characteristics. Linked To Adverse health effects In infants.4,5
Johnson cautioned that more research is needed to assess the effect of CMV infection on breast milk over the long term and to examine variations between individuals and between populations.[These questions] “It’s definitely impacting my work and how I see the future,” Johnson says. “There are things like fatty acids that vary widely from person to person. They’re influenced by genetics and diet and don’t appear to be tightly controlled by the mammary gland. And everyone has a different immune profile depending on their past exposures and vaccination records.”
More importantly, Johnson’s study highlights the existence of variability in breast milk, the potential for characterizing breast milk using multi-omics approaches, and how this variability may impact healthy infant development. Brit Goods“One of the most impressive things about this study is the variety of different types of data they were able to generate and the variety of different analyses they were able to do. It sounds so simple, but it’s really hard to pull off statistically effectively,” says Goods, a Dartmouth College bioengineer who was not involved in the study. Goods feels breast milk research is still in its early stages, and the scientific community needs to understand it better before applying the knowledge to the clinic. “For example, we don’t know how changes in protein composition relate to changes in the infants. This study is a really good example of where the field is going and will help us determine what questions to ask next.”
For Johnson, next steps include looking at preterm cohorts to see if the results observed in this study can be replicated, and to see if differences in breast milk composition are associated with better or worse clinical outcomes in preterm infants. She’s also interested in finding genetic variants associated with the breast milk metabolome that could help predict breast milk composition. “There are lots of cohorts that don’t have breast milk samples or breast milk metabolomic data, but they do have genetic information,” she notes.
References
1. Johnson KE et al. Human cytomegalovirus in breast milk is associated with breast milk composition and infant gut microbiota and growth.. Nat Community2024;15:6216.
2. Zuhair M, et al. Estimating global seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev Med Byroll2019;29(3):e2034.
3. Osterholm EA, Schleiss MR. Impact of breast milk-transmitted cytomegalovirus infection on premature infants: pathogenesis, prevention, and clinical impact. Rev Med Byroll2020;30(6):1-11.
4. Henrick B. M., et al. Bifidobacteria-mediated immune system imprinting during early childhood. cell2021;184(15):3884-3898.e11.
5. Kiu R, et al. Premature infants Clostridium tertium, Clostridium cadaverisand Clostridium paraputrificum Phylogeny: Genomic and evolutionary insights. Genome Bioevolution2017;9(10):2707-2714.
