What do mamas’ genes have to do with a babies’ guts?

A little bit about Human Milk and its benefits

For as long as we can remember, breastfeeding has been the ideal way to get all the nutrients to an infant (CDC, 2024). Across the world this has been the most natural way of feeding an infant; today there have been alternatives provided to help substitute breast milk. Having these options help mothers that are not able to breastfeed or would like to substitute.In the studies done by Gomes-Gallego et al and Jost et al, focused on the benefits that breastfeeding brings to a mother as well as the infant(Gomez-Gallego et al., 2016)(Jost et al., 2014). The long term benefits can be a bit difficult to determine past the infant stage. Various studies have focused on the gut microbiome, which is a bunch of microorganisms (bacteria) that are found in your body, that is seen in the maternal milks and how that impacts the infant’s gut microbiome (Gomez-Gallego et al, 2016). 

Researchers Babakobi et al., were able to find a link between the changes in the mother’s milk composition and how that change can impact the bacteria that is seen in the infants gut (Babakobi et al., 2020). Researchers focused on human milk oligosaccharides (HMO), a complex sugar that has beneficial effects on the development of a healthy microbiome for an infant. They found that the amount of proteins and lactose sugars that are essential for the composition of human milk can vary between women but is essential for the establishment of a healthy and mature gut (Pace et al., 2021)(Ballard & Marrow, 2013) . The composition of human milk is essential for the proper gut maturation and metabolic function as well as providing immune system development of infants. Human milk is made of fats, proteins, sugars and immune components, but what role do mothers’ genetics play in the composition of milk? Johnson et al., focuses on the relationship between maternal genotype, milk composition and infant health. Going into detail on how maternal genetics and gene expression of milk can lead to benefits in the development of the infant microbiome.

The Big Question!

How does the expression of certain genes from a mother influence the composition of breast milk and the infant’s gut microbiome?

Figure 1. This figure gives an overview of the steps that Johnston et al (2024) did to discover the correlation between mothers genes found in breastmilk and infant gut.

A little bit more about Mothers Genetics

Johnson et al. found that there are specific genes that directly influence the infant gut microbiome. By identifying the relationship between inflammation–related genes  and interleukin 6 (IL-6), a protein found in human milk that affects the immune system in the mammary gland, they were able to determine how they impact the infant directly through the consumption of breastmilk. To better understand what genes are involved, they performed an RNA sequencing, which is a technique that looks at certain nucleotides in a RNA strand, which helps identify which genes are generally seen to influence milk expression (Figure 1). They found an increased concentration of glucose, insulin, and interleukin 6 protein which were strongly correlated with the genes that are largely expressed in breastfeeding women. 

In addition, the interleukin protein concentration resulted from an inflammatory response which is expected in mammary glands. Looking at these protein concentrations a correlation was made between higher immune cells found specifically in human milk and the development of a healthy infant immune system. Gene expression was tested, which helps understand gene regulation and its implications to genes and variants of disease. This helped understand the roles that gene expression has in a certain locus, which impacts women’s health, like looking at genes that increase the risk for breast cancer. Gene expression shed a light on a very important component and that is HMOs!

Genetics and the composition of milk!

We know that HMOs that are found in breastmilk have a huge importance on the infants development. There were certain genes that were found to have a direct impact on the concentration of HMOs. For example, fucosyltransferase-2 (FUT2) gene expression influences the concentration of HMOs, finding this connection helps researchers understand how gene expression impacts HMO biosynthesis in the mammary gland. By doing this they were able to better understand that human milk contains many fats, proteins and carbohydrates, including vitamins, minerals and some immune components. As mentioned earlier on the importance of HMO, there are many factors like diet, environment, and overall health of a mother that can influence the composition of milk. Understanding the connection between specific genes and HMOs led to a further understanding of different developmental differences seen between the infants’ gut.  

How does this impact infants’ gut microbiome?

By determining what genetic component influences the composition of the breast milk it would allow further understanding of the development of the infant gut microbiome and the abundances of certain bacterias that are seen at 1 month vs 6 months of age. To see how genes impact the infant microbiome, Johnson et al. further tested the stool samples, and did metagenomic sequencing which allowed them to correlate genes within the mothers milk. They were able to reveal that fatty acid metabolism genes had an impact on the abundance of the bacteria Bifidobacterium in the first month of an infant, which promoted a particular bacterial species like B. infantis that has many benefits in the maturing of the infant immune system along with other functions. Compared to an infant at six months they saw an abundance of Escherichia spp which becomes more established as they infant eats solids. Focusing on the  link between  mammary inflammatory related gene expression with an abundance of healthy bacteria seen in the infants first months, along with the concentrations of HMOs in breast milk, further support the important role a mothers genes directly influences the infant gut microbiome. By further understanding the impacts that maternal genetics play on milk composition can lead to more research learning how they influence the child’s gut bacteria and immune system. 

Looking to the future

This article helps us understand the role that the mothers genes play in developing a healthy infant gut microbiome through the consumption of breast milk. Understanding the implications these genes have on milk composition leads to further questions, like how genes work with diet, environment and overall health of a mother. Although this can be a bit difficult in foreign countries, having a wider sample group with different backgrounds can help understand if there is a difference in composition of milk from different women or if there are certain age or racial groups that have differences due to their background and environment.  

How does genetics of women in different racial groups differ in relation to their milk composition and gut microbiome of their children?

Is there a link between the different microbiota of an infant due to genetics and diet?

Still need a bit more information?

Human Milk Microbiome| This video talks about the human microbiome and how they directly influence the infant gut and wellbeing. Finding that breast milk has its own microbiome and is unique to each mother. 

Human Milk Oligosaccharides (HMO)| This video goes further into the function of HMOs and their impacts on the infant’s body. How infants’ bodies use HMOs and why they are so important. 

Genetic and Physiological Factors Affecting Human Milk Production and Composition| There are many factors taken into consideration when looking at milk production and composition. This paper talks about extrinsic factors like environment and diet as well as intrinsic factors that would include stress, latching, genes.

References

Babakobi MD, Reshef L, Gihaz S, Belgorodsky B, Fishman A, Bujanover Y, Gophna U.; Effect of Maternal Diet and Milk Lipid Composition on the Infant Gut and Maternal Milk Microbiomes. Nutrients. (2020); 12(9):2539.

Ballard O, MorrowA L; Human Milk Composition: Nutrients and Bioactive Factors, Pediatric Clinics of North America, (2013) Volume 60, Issue 1, Pages 49-74, 

CDC: About breastfeeding  

 Gomez-Gallego C,  Garcia-Mantrana I, Salminen S,  Collado MC; The human milk microbiome and factors influencing its composition and activity, Seminars in Fetal and Neonatal Medicine,(2016) Volume 21, Issue 6, Pages 400-405, ISSN 1744-165X, 

Johnson KE, Heisel T, Allert M, Fürst A, Yerabandi N, Knights D, Jacobs KM, Lock EF, Bode L, Fields DA, Rudolph MC, Gale CA, Albert FW, Demerath EW, Blekhman R; Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome,Cell Genomics, (2024),Volume 4, Issue 10, 100638, ISSN 2666-979X,

Jost T, Lacroix C, Braegger CP, Rochat F, Chassard C. Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding. Environ Microbiol. (2014) ;16(9):2891-904.

Pace RM, Williams JE, Robertson B, Lackey KA, Meehan CL, Price WJ, Foster JA, Sellen DW, Kamau-Mbuthia EW, Kamundia EW, et al. Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities. Microorganisms. (2021); 9(6):1153.