By Don Olson
Around the turn of the last century, studies showed that babies who were breastfed had a lower mortality rate and fewer incidences of diseases than those who were bottle-fed. Since that time, there has been a growing research effort to understand what is special about human milk that provides infants with better health and protection against disease. This research, especially in recent years, has produced some remarkable findings. 1
The biggest breakthrough was the discovery of a family of molecules called human milk oligosaccharides (HMOs) in the early 1900s. Since then, 200 of these molecule families have been discovered and characterized. This diverse family of molecules acts as a sort of molecular “special ops” team that uses a range of strategies to encourage the growth of beneficial microbes in the infant’s gut and annihilate, discourage, thwart, and eject the harmful ones. This understanding has been helped by another even more remarkable and recent discovery that the human gut contains a host of different beneficial microbes and viruses—called by some the human ecosystem—that perform many functions critical to life. In fact, the number of microbes in our bodies outnumbers human cells by a factor of 10. However, since microbes are tiny compared to human cells, their mass is only a few pounds. Most of these are residents of the gut.
The Path of HMOs
How do the HMOs carry out their missions? To begin with, they must pass the stomach to reach their destination—the gut of the infant. The stomach wants to digest anything organic that flows into it, and since the HMOs are sugar molecules, one would think the stomach would make short work of them. However, data gathered by researchers shows that the great majority of HMOs survive the gastric acid and enzymes intact, most likely due to features of their structure and design. It seems paradoxical that an abundant portion (8%) of human milk, the sole source of nutrients to the infant, is indigestible, but now it is understood that this is a molecular design feature vital to the success of the HMOs in carrying out their mission.
What Do HMOs Do?
When they arrive at their destination, the structurally and chemically diverse HMO teams go to work on a variety of tasks.
- HMOs serve as a nutrient to beneficial bacteria but not to pathogens. The beneficial bacteria B. infantis consumes and thrives on HMOs, in contrast to pathogens such as E. coli which hardly grow at all on HMOs. This gives a competitive advantage to beneficial bacteria so they preferentially colonize and dominate the infant’s gut.
- HMOs snag harmful bacteria and give them a free ride to the baby’s diaper. HMOs accomplish this by acting as a decoy. A pathogen commonly gains access to a cell by binding to a receptor present on the surface of the cell wall. Once attached, the pathogen can colonize there and invade the tissue, causing disease. Some HMO structures sport the same receptors that fool the pathogen into attaching to the HMOs. Chained to the HMOs, the captured pathogen is then escorted downstream through the intestine and out of the infant’s body.
- HMOs block pathogens by attaching themselves to the mucosal surface of the intestine. Bode cites the HIV virus as an example: “In the breast-fed infant, mucosal surfaces are covered with high concentrations of HMO, which may block HIV entry via DC-SIGN [a binding structure on the cell surface used by HIV]. This may explain why mother-to-child HIV transmission through breastfeeding is rather inefficient with 80–90% of infants not acquiring infections, despite continuous exposure to the virus in milk over many months.” 2
- HMOs may help hinder infection by E. coli. In vitro (in the lab) studies show that when cultured human intestinal epithelial cell lines are incubated with one of the HMOs, the gene expression of several transferases that control the formation of glycan groups on the cell surfaces is diminished. The glycans are the receptors that E. coli bind with to gain access to and infect the cells. Thus, infection by E. coli is hindered. This is a more sophisticated epigenetic strategy than those already mentioned. Whether it happens in vivo (in the body) is yet to be determined.
HMOs Unique to Human Milk
Bode states in his paper that HMOs “are highly abundant in and unique to human milk.” Though oligosaccharides are present in cow’s milk, they are of a different mixture and comprise far less of the milk content than that found in human milk. For example, the oligosaccharide content of cow’s milk is less than 0.1% compared to 8% in human milk. Furthermore, the structural complexities of the HMOs are key. According to Barile and Rastall, “Comprehensive studies characterizing these carbohydrates support the idea that their structural complexity is the basis for a multitude of biological functions.” 3
Although the HMOs are a huge family of diverse complex structures, it is remarkable that the mammary glands churn them out by using only five simple sugar molecules as building blocks, something that infant formula-producing companies have made little headway in mimicking. The biochemistry of HMO assembly requires the action of a diversity of specific enzymes called glycosyltransferases as catalysts. The enzymes in turn require specific DNA sequences coded for their formation.
Relevance of HMOs to Our Christian Faith
Having in view this remarkable team of mission-oriented molecular wonders exquisitely designed to defend newborns against microbes, one can’t help but wonder how they came into existence, as well as why. Let’s take a look at these questions drawing from both a scientific and a Biblical perspective.
Numerous verses and passages in the Bible tell us that God is visible in his creation. Examples are Romans 1:20 and Psalm 19. Also, we are reminded in the Bible to look around at nature—at the birds, the fig tree, the fields, the diligence of the ant, the power of yeast, the beauty of lilies, and how our bodies are fearfully and wonderfully made. As well-known theologian R. C. Sproul put it, “creation is another theater of divine revelation.” During Biblical times, what one could observe in nature was limited to what could been seen with the naked eye. With the arrival of modern science, this limitation has been removed, revealing countless new wonders of God’s creation.
Modern science has provided us with a powerful new set of eyes with which we can peer deep into nature—from the mighty cosmos to the tiny living cell—and see the handiwork of God. It is not difficult to see God in the HMO story. When one considers the highly selective chemistry a mother’s mammary cells must have to produce this unique family of specific HMOs, it is truly remarkable. The number of different structures that are possible from combinations of the five sugar building blocks is in the millions. Yet these tiny cells are able to direct the chemistry along specific pathways to cleanly and efficiently stitch the sugar molecules together to produce this relatively small family of HMOs, with just-right structures and properties to serve the purpose of protecting infants. Furthermore, they are produced in high yield in the right amounts without any harmful side products. This is a feat that even master systhesis chemists have not been able to match. This capability requires an information-rich biochemical control system, which in this case is provided by DNA code, as well as what has been called a “glycocode.” 4 The elegant molecular logic that undergirds the HMO system is a marvel of God’s creation. As biochemist Russ Carlson wrote on oligosaccharides, “The multiple layers of information required to produce the right oligosaccharide structures in the cell from the bewildering complexity of possible structures supports the conclusion that the cell is ultimately the product of a mind.” 5
A question that occurred to me while writing this article was: why would God make this cocktail of powerful oligosaccharides unique to human milk? A verse that came to mind was Genesis 9:7 where God tells Noah’s family, “Be fruitful and increase in number; multiply on the earth and increase upon it.” And so they did. What other complex mammal numbers 7.5 billion on Earth? The boost in infant survival rate that HMOs provide certainly helps to fulfill God’s will in the multiplication of humankind.