Richard Peet, J.D., Ph.D.
THE THIRD MOST ABUNDANT COMPONENT IN HUMAN MILK ARE PREBIOTIC SUBSTANCES THAT SERVE AS FOOD FOR THE INFANT’S GUT MICROBIOTA.
The third most abundant component in human milk are prebiotic substances that serve as food for the infant’s gut microbiota. It is astounding to consider that highly nutritious human milk, designed through thousands of years of evolution to nourish a newborn infant, contains large quantities of a substance that, for the most part, are not directly used as food by an infant. After lactose and lipids, the third largest component of human milk consists of Human Milk Oligosaccharides (HMOs). HMOs are prebiotic substances. An expert panel of the International Scientific Association of Probiotics and Prebiotics (ISAPP) defined prebiotics as “a substrate that is selectively utilized by host microorganisms conferring a health benefit.” One important role of HMOs is to provide prebiotic food for “good bacteria” in the infant colon, and these bacteria in turn confer health benefits to the infant. It is generally accepted in the scientific community that when a baby is born, it does not have a microbiota, the collection of bacteria, archaea, viruses, and fungi found in and on the human body. The infant acquires its microbiota during and after birth. HMOs in human milk are utilized as a prebiotic food source by certain bacteria. Of particular importance, HMOs are metabolized by certain members of the bacterial genera Bifidobacterium and Lactobacillus. These good bacteria synthesize a wide variety of products
from HMOs, called metabolites, that benefit the infant. Some of the metabolites produced by good bacteria are short chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. These SCFAs create an acidic environment in the infant gut that inhibits the growth of pathogens. Furthermore, SCFAs are used as an energy source by cells that line infant’s intestine. Other metabolites produced by good bacteria in the gut include essential dietary vitamins and co-factors such as vitamin K, vitamin B, folate, thiamine, and riboflavin. The presence of prebiotic substances in human milk that, for the most part, are not directly used as a food source by the infant, but are used to nourish the infant’s microbiota, highlights the importance of consuming
prebiotic substances from the very start of life. It is now very evident that consumption of sufficient quantities of prebiotic substances throughout life is required to nourish a healthy microbiome and maintain health and wellbeing.
In addition to serving as prebiotic substances that shape a balanced and diverse infant intestinal microbiota, HMOs play other important roles in protecting the health of the infant. HMOs directly modulate intestinal epithelial cells thereby playing a role in developing a healthy immune response. HMOs serve as decoy receptors that prevent the adhesion of pathogens to host mucosal surfaces thereby reducing the incidence of infection. An emerging and very important role of HMOs in supporting the health of the infant is as a nutrient source for brain development. A component of some HMOs is a molecule known as Neu5Ac, also known as sialic acid (Sia). A healthy brain contains large quantities of Sia. Nutrition is regarded as a critical factor in early brain growth. Let’s learn more about the chemical components of human milk and then return to the important roles HMOs play in infant growth and development.
What are the chemical components of human milk? Human milk can be considered a complex living tissue with a composition that differs from woman to woman and changes over the course of lactation. Human milk contains the macronutrients and micronutrients essential for infant survival and development. In addition, human milk contains cells, microbes, microRNAs, bacterial constituents, antibodies, and immune cells. And of course, human milk contains HMOs. On average, human milk contains about 8 grams/liter protein, 41 grams/liter fat, 70 grams/liter lactose, and 5 to 15 grams/liter HMOs. With regard to HMOs, they comprise more than 150 different unique chemical structures. Each woman produces a subset of these different
chemical structures. HMOs are comprised of five monosaccharides arranged in different ways: glucose (Glc), galactose (Gal), N-acetylglucosamine (GlcNAc), fucose (Fuc) and Sia. All HMOs contain lactose at one end which is then elongated by addition of more monosaccharides during biosynthesis in the mammary gland. Lactose is a disaccharide comprised of Glc and Gal. About 50 to 80% of the HMOs contain the monosaccharide Fuc and about 10 to 20% of the HMOs contain the monosaccharide Sia.
Human milk is considered the optimal food for infants by the World Health Organization (WHO). The WHO recommends mothers exclusively breastfeed their infants for six months and continue to partially breastfeed up to at least two years. In the U.S., however, it is very difficult for women to breastfeed their newborns because the government, and most employers, do not provide sufficient maternity leave. Through no fault of their own, some women, and some babies, are not able to breastfeed. Infant formula is necessary under these circumstances. But many infant formula companies aggressively market their products and disregard the scientifically proven benefits of human milk for mother and infant. The maternal benefits of breastfeeding include protection from breast and ovarian cancer and cardiometabolic disorders. The scientific data is very clear that breastfed infants have lower rates of autoimmune diseases, allergy, and gastrointestinal problems in comparison of formula-fed infants. 1 Furthermore, breastfeeding reduces the risk of diabetes and obesity developing in adulthood. 2 And also of importance, research has shown that breastfeeding is associated with a higher intellectual quotient (IQ), income later in life, and school performance, compared to formula-fed infants. 3 Sia is essential for proper development of gangliosides and therefore critical in brain development
and function. Gangliosides are complex molecules that are most abundantly found in the cell membranes of neurons. Among the many functions of gangliosides, they are essential for the development, differentiation and repair of neurons as well as the proper formation of synapses (the junctions through which neurons communicate). Although humans synthesize Sia, it is HMOs containing Sia that are critical to providing sufficient quantities of Sia to support rapid brain development in the infant.
Does infant formula comprise Sia-containing HMOs? Bovine-based infant formulas contain Sia but much lower quantities than found in human milk. The Sia in bovine-based infant formula is bound to protein instead of other sugars and this may impact bioavailability when consumed by infants. The naturally occurring HMO 2′-fucosyllactose is found in some infant formulas but this HMO does not contain Sia. Infant formulas do contain prebiotics such as fructooligosaccharides, galactooligosaccharides, or polydextrose. Although these prebiotics stimulate the growth of good bacteria in the infant gut, they are not naturally found in human milk and are not Sia-containing HMOs. Biosynthesis of HMOs in human cells is poorly understood and is a very active area of scientific research. In the future, HMOs may be manufactured in genetically engineered microorganisms, purified, and included in infant formula. The lack of naturally occurring HMOs, especially Sia-containing HMOs, in infant formula is an example of how infant formula is an imperfect substitute for human milk.
The presence of large quantities HMOs in human milk, prebiotic substances that, for the most part, cannot be directly used by an infant as a food source, but are a food source for the infant’s microbiota, underscores the critical importance of nourishing and sustaining the good microbes in our gut to sustain our health and wellbeing. After millions of years of co-evolution of humans, and our ape ancestors, with the microorganisms that live in and on our bodies, we now depend on each other. The microbes depend on humans for food and shelter. Humans depend on our microbiota to produce metabolites that are critical for our health and wellbeing. It is critically important that we help newborns get a great start in life with access to the critically important prebiotics, known as HMOS, found in human milk.
- Vieira et al., Breastfeeding and autoimmunity: Programming health from the beginning, American Journal of Reproductive Immunology 79(1):e12778. doi: 10.1111/ aji.12778
- Mamun et al., Breastfeeding is protective to diabetes risk in young adults: A longitudinal study, Acta Diabetologica 52(5): 837-844 (2015) doi: 10.1007/s00592-014-0690-z
- Victora et al., Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: A prospective birth cohort study from Brazil, The Lancet Global Health 3(4): e199–205–e205. doi: 10.1016/ S2214-109X(15)70002-1199–205–e205. doi: 10.1016/ S2214-109X(15)70002-1